Category Archives: Regenerative Medicine

C-CAR039 showed positive efficacy and safety data in patients with relapsed or refractory B-cell non-Hodgkin lymphoma.

Officials with the FDA have granted both Regenerative Medicine Advanced Therapy (RMAT) Designation and Fast Track Designation to C-CAR039, a novel autologous bi-specific chimeric antigen receptor (CAR) T-cell therapy, for the treatment of patients with relapsed or refractory (r/r) diffuse large B cell lymphoma (DLBCL).

C-CAR039 targets both the CD19 and CD20 antigens, and early results from an investigator-led trial demonstrate positive efficacy and safety data in patients with r/r B-cell non-Hodgkin lymphoma. As of April 20, 2021, 34 patients received the therapy, 28 of whom were eligible for safety analyses and 27 of whom were evaluable for efficacy analyses. Patients median age was 55.5 years and 75% had cancer of Ann Arbor stage 3/4. Participants had a median of 3 prior lines of therapy and bridging therapy had been given to 17.9% of patients.

According to a press release, the best overall response rate was 92.6%, with a complete response rate of 85.2%. Patients had a median time to response of 1 month and at a median follow-up of 7 months, 74.1% of patients were still in complete remission. Furthermore, the 6-month estimated progression-free survival rate was 83.2%.

This is great news for CBMG that the FDA has granted C-CAR039 both RMAT and fast track designations based on its potential to increase objective and complete response rate in r/r DLBCL, said Tony Liu, chairman and CEO of Cellular Biomedicine Group, in the press release. The clinical data based on our clinical trials in China continue to support the hypothesis that C-CAR039 is the best-in-class CAR T asset for patients in this indication.

Cytokine release syndrome (CRS) was reported in 96% of patients, 92% of which was grade 1/2. Only 1 patient had grade 3 CRS. Immune effector cell-associated neurotoxicity syndrome occurred at grade 1 in 2 patients and no grade 2 or higher neurologic events were reported, according to the press release. The researchers will continue to evaluate patients with longer follow-up.

Separately, the FDA Office of Orphan Products Development granted an Orphan Drug Designation to C-CAR039 for the treatment of follicular lymphoma in June 2021. The Investigational New Drug application was cleared by the FDA on December 10, 2021.

We are working toward initiating 1b/2 trials for C-CAR039 in the US soon, Liu said in the press release. And we will work closely with the FDA to seek the best path forward to deliver the drug to patients in the US and EU.

REFERENCE

CBMG Receives FDA Regenerative Medicine Advanced Therapy and Fast Track Designations. News release. CBMG; January 12, 2022. Accessed January 13, 2022. https://www.cellbiomedgroup.com/newsroom/fda-rmat?lang=en

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FDA Grants Regenerative Medicine Advanced Therapy, Fast Track Designations to Novel CAR T-Cell Therapy for Relapsed, Refractory B-cell Non-Hodgkin...

NOW IS THE TIME TO SUPPORT REGENERATIVE MEDICINE

TORONTO, Jan. 19, 2022 /CNW/ - As The Government of Ontario prepares its 2022 Spring Budget, OIRM is raising awareness of the massive losses expected if critically important sector funding is not continued.

At OIRM, we understand the unprecedented financial challenges facing Ontario, particularly in the healthcare sector, and this makes it even more vital that we take full advantage of the vast potential of Ontario's newly established Regenerative Medicine ecosystem to address Finance Minister Bethlenfalvy's key priorities:

Ontario's innovative stem cell scientists are already saving lives, including state-of-the-art treatments for COVID recovery, as Sharon Charlebois can attest. After being admitted into ICU with COVID-19 at The Ottawa Hospital, Sharon attributes her survival to the stem cell treatment she received. Read Sharon's fully story here.

Stem cell science originated in Toronto 50 years ago with the ground-breaking discovery by Doctors James Till and Ernest McCulloch; a remarkable contribution to our provincial, and national, legacy.

At a time when the unprecedented commercial value of stem cell technologies are just beginning to be realized, Ontario's stem cell innovators are now at a crossroads. Without ongoing funding, Ontario stands to lose it competitive advantage and the opportunity to benefit from the burgeoning Regenerative Medicine commercial sector.

Catalyzed by an initial $25M investment from the provincial government in 2015, OIRM has since generated $174.5M (6.9-fold ROI) in leveraged funding and invested in cutting-edge technologies that generated an additional $332M (13-fold ROI) in Series A investment. OIRM support was a key factor in the path leading to the creation of BlueRock Therapeutics, one of the greatest Canadian biotech success stories, which was acquired by Bayer in 2019 for $1B (40-fold ROI) and is now a leading engineered cell therapy company.

"BlueRock invested in the Ontario ecosystem because of work that OIRM had supported from Dr. Michael Laflamme (UHN). It was really the strength of the science under OIRM's guidance, in my view, that led to our decision to launch and build BlueRock Therapeutics in the Toronto-area. OIRM's support was critical to getting a small biotech launched. I would like to see that funding envelope increased to give the Institute the ability to bring these programs to a later phase of value creationsomething that would have the added benefit of creating more confidence in potential investors."- Dr. Bob Deans, Chief Technical Officer, BlueRock Therapeutics 2017-2020

It is reasonable to expect more opportunities like BlueRock to develop if Ontario continues to nurture stem cell research and innovation. Ontario is staring at a $1B economic opportunity by funding Regenerative Medicine advancements. But in 2020, while the California Institute for Regenerative Medicine was refunded at $5.5B USD, here at home the funding for OIRM was removed as part of a cost-cutting exercise, and unfortunately before a glowing reportfrom a blue-ribbon international review panel that recommended renewed funding for OIRM.

OIRM is imploring government to reconsider its position and continue funding stem cell advancements in Ontario. An investment of $25M over 5 years will yield massive returns for Ontario.

At no point in history have public health and economic recovery been simultaneously prioritized by the provincial government as urgently as right now. Medical treatments are evolving rapidly, and if made-in-Ontario stem cell research remains a priority for The Government of Ontario, there is good reason to feel hopeful about the future.

OIRM is a passionate champion for healthcare providers and their patients as we build a healthier future for Ontario, Canada, and the world.

SOURCE Ontario Institute for Regenerative Medicine

For further information: For media inquiries, please contact: Sandra Donaldson, Vice President and Chief Operating Officer, Ontario Institute for Regenerative Medicine, E: [emailprotected], T: 647-926-1228

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Ontario Institute for Regenerative Medicine (OIRM) - Urgent Appeal to The Government of Ontario - Canada NewsWire

Jan. 13, 2022

Health and innovative thinking was the focus of this years Founders Day Convocation at Illinois Wesleyan University.

A recording of the virtual Convocation may be viewed here.

Illinois Wesleyan President S. Georgia Nugent spoke of the motives that led to the founding of the University in 1850 and their relevance today, as well as the annual intellectual theme of Health, Healing and Humanity.

A theme that obviously could not be more relevant today, as we see these three inextricably intertwined in the context of the Coronavirus pandemic, she said.

Biomedical researcher William Murphy, a 1998 IWU Physics and math graduate, gave the keynote address titled Mimicking Nature to Create New Technology.

Murphy spoke about how his experience as a Titan helped shape his future career in biotechnology. He shared examples of his research efforts to create regenerative medicine based on materials already found in nature.

You are fortunate to be enrolled at a yes, and institution, said Murphy. You dont have to choose to become only a physicist, or only a chemist, or only a business student. You can also be a baseball player or a musician. One can engage in all of these opportunities at once to build what will become the foundation for your lifes journey.

He reminded students that every course of study can make an impact on the world.

I hope Ive convinced you today that there is so much more to discover and leverage in nature and that all disciplines can contribute to the future of biotechnology, he said. Your IWU education is preparing you wonderfully to make breakthrough discoveries and turn them into real-world products.

By Julia Perez

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Founders' Day Speaker: Breakthrough Discoveries Lead to Real World Applications - Illinois Wesleyan University

SUWANEE, GA, Jan. 18, 2022 (GLOBE NEWSWIRE) viaNewMediaWire SANUWAVE Health, Inc. (SNWV), a leading provider of next-generation wound care products, announced it will hold a conference call on Wednesday, January 19, 2022, at 9:00 am ET to discuss its recent business activity, provide an update on SEC filings and detail strategic initiatives.

Telephone access to the live call will be available by dialing the following numbers:

Toll Free: 1-877-407-0784

International: 1-201-689-8560

A replay of the call can be accessed through February 2, 2022, at:

Toll Free: 1-844-512-2921

International: 1-412-317-6671

Replay Passcode: 13726404

About SANUWAVE Health

SANUWAVE Health (SNWV) is focused on the research, development, and commercialization of its patented,Energy Firstnon-invasive and biological response-activating medical systems for the repair and regeneration of skin, musculoskeletal tissue, and vascular structures.

SANUWAVEs end-to-end wound care portfolio of regenerative medicine products and product candidates help restore the bodys normal healing processes. SANUWAVE applies and researches its patented energy transfer technologies in wound healing, orthopedic/spine, plastic/cosmetic, and cardiac/endovascular conditions. For more information, please visit.www.SANUWAVE.com.

Investor Relations ContactSANUWAVE Health, Inc.Kevin Richardson IIChairman and Chief Executive Officer978-922-2447investorrelations@SANUWAVE.com

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SANUWAVE Health to Host Conference Call and Provide Business Update - OrthoSpineNews

By Deborah Borfitz

January 19, 2021 | Eight years ago, an international team of researchers proposed that the term proteoform be adopted to describe the vast number of forms of protein products from our genesincluding changes due to genetic variations, alternative RNA splicing, and post-translational modificationsto reduce the semantic-related ambiguity in the study of proteins. Since these proteoforms can be turned on or off, understanding them with absolute molecular precision is required to demystify the world of how proteins function and unlock the future of human biology, says Neil Kelleher, professor of molecular biosciences, chemistry, and medicine at Northwestern University and faculty director of Northwestern Proteomics, as well as a world-renowned proteomics pioneer.

To that end, the nonprofit Consortium for Top-Down Proteomics recently proposed the Human Proteoform Project to generate a definitive reference set of the proteoforms produced from the genome. This will become a seminal moment in science, Kelleher says, and the initiative is the next obvious step now that the Human Genome Project has provided the blueprint for how proteins get made.

Details of the proposal were recently published in Science Advances (DOI: 10.1126/sciadv.abk0734). The end goal is creation of a Human Proteoform Atlas, a high-resolution reference proteome that will be public and available to all, including the many proteomics companies recently advancing in the private sector. It is possible to accomplish this ambitious project over the next decade, Kelleher says.

Mapping of the open frontier of our proteome would have wide-ranging implications, he adds. The impacts would improve and elevate the return on investment in clinical proteomics, chemical proteomics and drug development, regenerative medicine, and next-generation proteomics like single-molecule protein sequencing.

Most people have more than a passing interest in proteins whether they are aware of it or not, says Kelleher, because proteins are involved in all human diseases. The Human Proteoform Project would enable earlier and more precise detection of those diseases.

That could help explain the rush of money from venture capitalists, institutional investors, and Wall Streetby some accounting, roughly $3 billion in the past 18 months aloneinto proteomics, says Kelleher. The recipients include biotechnology companies focused on promising technologies such as single-cell proteomics techniques, single-molecule proteoform analysis, and single molecule protein sequencing.

In some sense, they are vying to become the Illumina of proteomics, he says, replicating the success of one of the biggest next-generation companies made possible by the Human Genome Project. In the few years afterward, that publicly funded initiative stimulated the creation of about 300,000 new jobs as the price of sequencing genomes plummeted.

Proteomics is on a path to become equal to genomics in terms of economics and benefits for the future of human health, says Kelleher. With government support, the proteomics ecosystem could grow tenfold. A pre-competitive proteomics initiative launched now could therefore have accelerated impact relative to the Human Genome Project because of work already underway in the private sector.

Life Of Their Own

Northwestern Proteomics, the leader in top-down proteomics, is certainly interested in advancing the Human Proteoform Project. The 60-scientist group maintains the proteoform informatics platform that will serve as initial versions of Human Proteoform Atlas, Kelleher shares. Details about creation of the web-based repository just published in Nucleic Acids Research (DOI: 10.1093/nar/gkab1086).

The field has long been dominated by bottom-up proteomics, based on mass spectrometry, which generates about $5 billion per year in economic activity. Northwestern Proteomics, and the Consortium for Top-Down Proteomicswhere Kelleher serves as president of the board of directorsis concerned with systematic discovery of intact proteoforms with all their molecular parts.

Even today, proteoform is probably a familiar term to a minority of scientists, he says. Structural biologists may have concluded that study of the proteome has reached its pinnacle now companies like AlphaFold (developed by Googles sister company DeepMind) have figured out how to fold proteins via computer.

But the proteoforms, what Kelleher describes as all the decorations that occur in life, remain largely unknown. As an example, he points to the eyeballs, which yellow and get diseased with age because certain protein molecules dont get repopulated.

Its the same scenario across all major disease areas, he says, including cardiology, oncology, and, most especially, neurology and neurodegeneration. Clinicians even call them proteinopathies, or diseases of proteins in your brain.

By mapping out what proteins are created from the bodys 20,300 human genes, the Human Proteoform Project will elevate the whole ecosystem for biomedical research and for clinical practice, says Kelleher. There is a proteoform family for every human gene, and proteoforms have a life of their own. They can be activated or repressed after they are produced, and their diversity varies widely in our different cell types in unknown ways.

Millions of unique proteoforms are created across the genome due to genetic variation, modification, or alternative splicing, making it an almost unfathomably large undertaking. All of this is radically open science, Kelleher says, from which all humankind stands to benefit.

Top-Down Strategy

The Consortium for Top-Down Proteomics launched in 2012. It now has 400 members from around the world advocating for a government role in funding the Human Proteoform Project, says Kelleher.

The proposed approach is different from mainstream proteomics, which captures about 10% of the human proteome, he continues. He likens the bottom-up strategy to stamp collecting where proteoforms are a collection of stamps that get shredded into about 50 pieces each, all about the same size, which then get blown about. Scientists must get down on the floor to collect all the little pieces and try to put the stamps (proteoforms) back together.

In contrast, a top-down strategy determines the precise weight of each stamp (proteoform), all of which are slightly different, says Kelleher. The stamps would also have distinct structural attributes. Scientists then controllably break the stamps into pieces to achieve 100% molecular precision for each one.

The board of directors of the Consortium for Top-Down Proteomics is now forming an advisory board to broaden the advocacy base for the Human Proteoform Project, Kelleher reports. It will include current supporters of the consortium as well as scientific leaders.

The consortium has members from academic institutions, corporations, and government agencies worldwide, and its work is supported by sponsorships from Thermo Fisher Scientific, Bruker, SCIEX, Pfizer, and Agilent.

Players in the proteomics space include big players (e.g., Thermo Fisher Scientific, Bruker, Agilent, Waters, and Sciex), numerous small- to mid-size companies providing tools and services, and a growing assortment of small biotech companies attracting venture capital, says Kelleher. Additionally, many biopharmaceutical companies are already using top-down proteomics every day. Half of the whole pipeline of new drugs are proteins, so that means proteoforms.

Scaling The Atlas

The existing proteoform atlas, residing on the consortiums website, contains a couple hundred thousand proteoforms. Northwestern Proteomics also has 50,000 unique human proteoforms from five human tissues, Kelleher says.

As envisioned, technology development over the first three to four years of the project will focus on advancing mass spectrometrya linear extension of the current state of play in top-down proteomics, says Kelleher. After that, the crystal ball as to what disruptive platforms could emerge gets a little hazy which is why were excited by all those biotech proteomic entrepreneurial companies.

The community will need to expand its team of proteoform informaticians to perhaps 40 or 50 software engineers, he adds. The Consortium for Top-Down Proteomics also has a working group of about 40 computer geeks around the world currently being funded by an assortment of small grants.

But the project cant realistically happen on the scale proposed without major financial support from federal governments or foundations, Kelleher notes. The initial ask, now that the framework for the project has been outlined, is on the order of $100 million a year in support. For perspective, the Human Genome Project required approximately $4 billion in public investment over about a decade.

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Human Proteoform Project Could Be Biology's Next Moonshot - Bio-IT World

J Oral Maxillofac Pathol. 2018 Sep-Dec; 22(3): 367374.

1Department of Oral Pathology, MMNG Halgekar Institute of Dental Science, Belagavi, Karnataka, India

2Center for Incubation, Innovation, Research and Consultancy, Jyothy Institute of Technology, Bengaluru, Karnataka, India

3Department of Oral Pathologist, Chaitanya Dental Clinic, Bengaluru, Karnataka, India

4General and Laparoscopic Surgeon, SSNMC Hospital, Bengaluru, Karnataka, India

1Department of Oral Pathology, MMNG Halgekar Institute of Dental Science, Belagavi, Karnataka, India

2Center for Incubation, Innovation, Research and Consultancy, Jyothy Institute of Technology, Bengaluru, Karnataka, India

3Department of Oral Pathologist, Chaitanya Dental Clinic, Bengaluru, Karnataka, India

4General and Laparoscopic Surgeon, SSNMC Hospital, Bengaluru, Karnataka, India

Received 2018 Sep 3; Accepted 2018 Sep 6.

This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

Regenerative medicine encompasses new emerging branch of medical sciences that involves the functional restoration of tissues or organs caused by severe injuries or chronic diseases. Currently, there are two contending technologies that can repair and restore the damaged tissues, namely platelet-rich plasma (PRP)- and stem cell (SC)-based therapies. PRP is a component of blood that contains platelet concentrations above the normal level and includes platelet-related growth factors and plasma-derived fibrinogen. Platelets are the frontline healing response to injuries as they release growth factors for tissue repair. SCs, on the other hand, are the unspecialized, undifferentiated, immature cells that based on specific stimuli can divide and differentiate into specific type of cells and tissues. Differentiated SCs can divide and replace the worn out or damaged tissues to become tissue- or organ-specific cells with specialized functions. Despite these differences, both approaches rely on rejuvenating the damaged tissue. This review is focused on delineating the preparation procedures, similarities and disparities and advantages and disadvantages of PRP- and SC-based therapies.

Keywords: Platelet-rich plasma, regeneration, stem cells, treatment

Regenerative medicine is a major part of the rapidly emerging biomedical research over the last decade which mainly involves the development of new therapeutic strategies resulting in greater advancement in the field. These recent biomedical approaches have provided the tenacity for medical community to look for alternatives to conventional therapies. Among the several therapeutic strategies available, the use of platelet-rich plasma (PRP) and stem cell (SC) represents the mainstream technologies to repair and rejuvenate the damaged tissue caused due to injury or chronic diseases.[1] PRP is the component of the blood (plasma) which contains five times higher concentrations of platelets above the normal values, i.e., PRP is the volume of autologous plasma that has the platelet concentration above the baseline.[2] Platelets are the tiny components of blood that are rich in growth factors and play a crucial role by forming blood clots during injury. It is a well-known fact that wound healing of damaged tissues depends on the platelet concentrations. PRP acts by nurturing those cells that can heal on their own or can augment the healing process by the resolution of damaged tissues. One of the widely used applications of PRP is in the regeneration and reconstruction of skeletal and connective tissues in the periodontal and maxillofacial diseases and in sports-related injuries.[3,4] Unlike PRP, SCs are the primitive cells that are obtained either from embryos or from the adult tissues. SC has the capacity of self-renewal and can differentiate into as many as 200 different cell types of the adult body.[5] Besides these properties, SC also produces certain growth factors and cytokines that accelerate the healing process at the site of tissue damage. Therapeutic applications of SC include treating many degenerative and inflammatory conditions by replacing the damaged cells in virtually any tissue or organ, where PRP applications serve no benefit.

Although both PRP- and SC-based therapies are destined to perform similar functions in restoring the damaged tissue to function normally, there exists a vast difference in their preparation procedures and their functionality []. SC is isolated from the adult tissues and cultured in sophisticated settings and requires several weeks to grow before they could be used for therapeutics. Contrary to SC, preparation of PRP is simple and involves rapid separation from blood and does not contain SCs for therapeutics per se. Furthermore, compared to SC-based therapies, the curative potential of PRP is considerably lower and regenerative potential is limited to the cells present in such tissues. Due to the similarity in function and the rapid preparations of PRP, several clinicians persuade patients to prefer PRP-based approaches citing that it is similar to SC-based therapies. Considering the existence of such a paradigm between the use of PRP- and SC-based technologies, future research should focus on understanding and clearly defining the molecular mechanism in tissue regeneration. In addition, efficacy and the perseverance of preparative methods, consensus in the preparation methods among different research groups for clinical applications and the significance of such technologies as a substitute for conventional therapies should be delineated and appropriately implemented.[4]

The differences between platelet-rich plasma and stem-cell therapy

The term PRP was introduced in the 1970s to describe the autologous preparations and enrichment of platelets from plasma concentrate.[6] Platelets also known as thrombocytes are produced from megakaryocytes in mammalian bone marrow.[7] They form a first line of cellular defense response following damage to vascular and tissue integrity and play a crucial role in homeostasis, innate immunity, angiogenesis and wound healing.[8,9,10] Under normal conditions, the typical blood samples contain approximately 94% of red blood cells (RBCs), 6% of platelets and 1% of white blood cells. The whole purpose of enriching for PRP is to reverse the RBC-to-platelet ratio to achieve 95% platelets and 5% of RBCs.[11] Enriched fraction of PRP is known to contain high level of growth factors and cytokines that promote tissue regeneration and healing and also reported to be effective in tissue reparative efficacy.[12]

The primary roles of platelets are to form aggregated and also contribute to homeostasis through adhesion, activation and aggregation. Previously, platelets were thought to have only hemostatic activity. However, recent advancement has provided a new perspective on platelet function in regulating inflammation, angiogenesis, SC migration and cell proliferation.[6] Although many studies have supported the beneficial effects of using PRP, the Food and Drug Administration approval for injections of PRP is still under consideration. The only adverse reaction reported is transient pain and localized swelling after injections, but the overall adverse reactions being very low. Further studies are required to assess the efficacy of use of PRP for therapy and its possible long-term adverse reactions.

Platelets play an important role in healing at the site of injury. The increased number of platelets results in increased number of secreted growth factors, thereby increasing the healing process. This phenomenon is attributed as it promotes mitogenesis of healing capable cells and angiogenesis in the tissues. Along with the presence of growth factors, they also contain adhesion molecules that include fibrin, fibronectin and vitronectin which help promote bone formation.[13,14] PRP preparations also play a role in revascularization of damaged tissue by promoting cell migration, proliferation, differentiation and stabilization of endothelial cells in new blood vessels. PRP also restores damaged connective tissue by promoting the migration, proliferation and activation of fibroblasts.[15,16] Platelets also host a vast reservoir of over 800 proteins which when secreted act upon SCs, fibroblasts, osteoblasts and endothelial and epithelial cells.[12] The main purpose of using PRP for therapeutics originated from the idea to deliver the growth factors, cytokines and -granules to the site of injury, which acts as cell cycle regulators, and promote healing process across variety of tissues.[8]

The PRP preparations are known to contain many growth factors, chemokines and cytokines [] which induce the downstream signaling pathways that ultimately lead to synthesis of proteins necessary for collagen, osteoid and extracellular matrix formation.[17] PRP also has numerous cell adhesion molecules including fibrin, fibronectin, vitronectin and thrombospondin that trigger the assimilation of osteoblasts, fibroblasts and epithelial cells. Apart from its role in structural and functional healing, PRP preparations are also been implicated in the reduced use of narcotics, improved sleep and reduction in pain perception.[6,18,19]

The components of platelet-rich plasma and their functions

Preparation of PRP for regeneration of tissues includes three sequential steps blood collection, PRP separation and PRP activation. Briefly, blood is collected using the anticoagulant agent preferably using acid citrate dextrose. The blood is then centrifugation using highly variable protocols with varying time (420 min), velocities (1003000 g), temperature (12C26C) and cycles of centrifugation (1 or 2 cycles). Due to these variable protocols, the platelet concentrations are enriched anywhere between 5 and 9 times. After centrifugation, the blood is separated into three layers the bottom layer (RBCs), middle layer (platelets and white blood cells) and top layer (plasma with gradient of platelet concentrations) [].[11,15]

The procedure of separation of platelet-rich plasma from the venous blood

Considering different parameters and clinical applications, PRP is further classified base on four categories: activated, nonactivated, leukocyte rich and leukocyte poor. Activated PRP is prepared with calcium chloride with or without thrombin, which leads to release of cytokines from the granules in platelets. Nonactivated PRP preparations include platelet contact with intrinsic collagen and thromboplastin, which activate the platelets within connective tissue. In addition, the presence of leukocytes plays a role in inhibiting bacterial growth by improving soft-tissue healing, which would have been hindered by infection.[13] Magalon in 2016 proposed a DEAP classification which is based on dose, efficiency, purity and activation of platelets.[6] Further studies have been carried out to characterize and classify PRP based on preparation (centrifugation and use of anticoagulant), content (platelets, leukocytes and growth factors) and clinical applications. Studies by Dohan Ehrenfest et al. have proposed PRP classifications based on the presence and absence of leukocytes and fibrin architecture.[20]

Pure PRP: Preparations show low-density fibrin network after activation

Leukocyte- and PRP: Preparations contain leukocytes and exhibit low-density fibrin network after activation

Pure platelet-rich fibrin: Preparations lack leukocytes and have high-density fibrin network and exist in activated gel form

Leukocyte- and platelet-rich fibrin: Preparations have leukocytes with high-density fibrin network.

Over the last few years, the use of PRP as a therapeutic tool has made a significant advancement in the field of regenerative medicine particularly in the field of wound healing and skin regeneration, dentistry, cosmetic and plastic surgery, fat grafting, bone regeneration, tendinopathies, ophthalmology, hepatocyte recovery, esthetic surgery, orthopedics, soft-tissue ulcers and skeletal muscle injury and others.[8]

As PRP contains high concentrations of growth factors, it is widely used for hair regrowth. These growth factors promote hair regrowth by binding to their respective receptors expressed by SCs of the hair follicle bulge region and associated tissues.[12]

The application of PRP in dermatology has increased in tissue regeneration, wound healing, scar revision and skin rejuvenating effects. PRP has rich source of growth factors that promote mitogenic, angiogenic and chemotactic properties; it has been used for the treatment of recalcitrant wounds. In cosmetic dermatology, PRP is known to stimulate human dermal fibroblast proliferation and increase type I collagen synthesis. In addition, injections of PRP into deep dermal layers have induced soft-tissue augmentation, activation of fibroblasts, new collagen deposition, new blood vessels and adipose tissue formation. Studies have also shown that PRP along with other techniques has improved the quality of the skin and leads to an increase in collagen and elastic fibers.[6]

PRP has also been used predominantly for musculoskeletal regeneration caused during sports injury. Acute hamstring for injuries accounts for approximately 29% of all sports-related injuries where PRP-based treatments have shown beneficial effects. Patellar tendinopathy also known as jumper's knee is the most common cause of anterior knee pain among athletes. Application of PRP is known to promote repair and reduce inflammation.[6] Achilles tendinopathy is another sports injury associated with severe pain and swelling at the tendinous insertion site. The rupture might get worse without proper treatment. Currently, muscle-strengthening exercise and anti-inflammatory medications are the only treatment options. The use of PRP was proposed as a treatment option.[13]

Osteoarthritis is one of the most common knee disorders which are commonly seen in elderly people due to cartilage damage and inflammatory changes. Several meta-analysis conducted on the these patients using both leukocyte-rich and leukocyte-poor PRP has displayed the benefits in favor of using PRP for osteoarthritis. PRP is known to stimulate chondrocytes and synoviocytes to produce cartilage matrix. In rotator cuff tear, which is the most common cause of shoulder disability, the inclusion of PRP-based therapy has beneficial effects for tendinous injuries. However, further clinical trials and metadata analysis are required for the clinical use of PRP as effective treatment technologies.[13] Apart from these diseases, PRP has also known to suppress the growth of particular species of bacteria such as Staphylococcus aureus.[21] It is also shown to improve endometrial thickness in patients undergoing in vitro fertilization treatment.[22]

In conclusion, there is an increase in the evidence that shows the beneficial use of platelet-based applications in tissue regeneration. However, there is considerable debate on the effectiveness of platelet-based applications, especially between human- and animal-based studies which could be due to the methodological differences among different research groups. There is a tremendous possibility for exploration in regenerative medicine which could use PRP for potential therapeutic applications.

The major advantage of the use of PRP for therapeutic applications is the immediate preparation of PRP, which does not require any preservative facilities. PRP is considered safe and natural as the preparation involves using own cells without any further modifications. This also ensures that the preparations do not elicit immune response. Since the preparations are from the same person, the chances of getting the bloodborne contaminations are minimized. As a large number of populations succumb to musculoskeletal injuries or disorders, application of PRP-based therapies has shown promising results.[11,23]

The use of PRP as such does not have major demerits. However, under certain circumstances, PRP applications can result in injection-site morbidity, infection or injury to nerves or blood vessels. Scar tissue formation and calcification at the injection site have also been reported. Some patients have also experienced acute ache or soreness at the site of injection and also in the muscle or deeper areas such as the bone. Patients with compromised immune system or with predisposed diseases are more susceptible to infection at the injured area. Studies have reported allergic reactions among few individuals who have taken PRP-enriched fractions. Since PRP is given intravenously, the chances of damaging the artery or veins which could result in blood clot exist. Studies have also advised against using PRP-based therapies among individuals with a history of heavy smoking and drug and alcohol use and patients diagnosed with platelet dysfunction syndromes, thrombocytopenia, hyperfibrinogenemia, hemodynamic instability, sepsis, acute and chronic infections, chronic liver disease, anticoagulation therapy, chronic skin diseases or cancer and metabolic and systemic disorders due to the complications associated with the PRP-based treatment.[11]

Recent advancement in the SC research has emphasized on the use of adult SC (ASC)-based therapies, which were not cured by conventional medicines. Tissue-resident adult progenitor SCs have clinical importance due to their potential cell sources for transplantation in regenerative medicine and cancer therapies. The ability for indefinite self-renewal and multilineage differentiation into other types of cells represents SCs, which offers great promise in replacing the nonfunctional or lost cells to regenerate damaged or diseased tissues.[24] The use of small subpopulation of adult stem or progenitor cells from tissues or organs from the same individual provides the possibility of stimulating those in vivo differentiation or cell replacement and gene therapies with multiple applications in humans without the risk of graft rejection. Research on tissue-resident SCs has explored the clinical interest in cell replacement-based therapies in regenerative medicine and cancer therapies.[25]

Based on their origin, SCs are divided into two types embryonic SCs (ESCs) and ASCs. ESCs are derived from epiblast of the blastocyst from which many tissues of embryo arise, whereas ASCs are localized in adult organs [] where these cells function to replace damaged cells during tissue regeneration.[26,27] SCs are further classified into four types based on their transdifferentiation potential which include totipotent, pluripotent, multipotent and unipotent SC.[24] ESCs are known to have totipotent and pluripotent in nature and have the ability to differentiate into cells of three germ layers endoderm, mesoderm and ectoderm.[28] ASC is multipotent and can give rise to differentiated cells of anyone germ layer.[29] Unipotent SCs arise from multipotent cells and are dedicated to differentiate into specific type of tissue, for example, precursors for cardiomyocytes present in human heart or satellite cells characteristic for skeletal muscles are dedicated to differentiate into specific tissue.[30]

Source and Type of cells produced from a normal adult stem cells

The use of SCs for therapeutic purposes was proposed as early in the 1960s because of their inherent ability to differentiate into multiple cell lines.[17] This requires careful isolation and culturing which has to be done in aseptic condition. SCs are extracted either from bone marrow or fat tissue and are sometimes used in conjunction with platelets. Once isolated, SCs can retain their ability to transform into a variety of cell types. So far, there is no standardized procedure to isolate and to characterize SCs; however, specific markers are available to identify them.[31] Mesenchymal SCs (MSCs) are extensively studied cell types in regenerative medicine due to their immunomodulatory properties.[32] Studies have shown that MSC has the capacity to differentiate into osteocytes, adipocytes, myocytes and cells of chondrogenic lineage.[17] MSCs express markers that include CD73, CD90 and CD105 (endoglin) but not CD11b, CD14, CD19, CD34, CD45, CD79a and human leukocyte antigen Class II.[33] Hematopoietic SCs express two important hematopoietic markers, i.e., CD45 and CD34.[34] Certain markers have been used as pluripotent markers such as OCT4, NANOG and SOX2. OCT4 is a transcriptional factor involved in early embryogenesis and very much essential for maintenance of pluripotency of SCs.[35] NANOG is a transcription factor and is involved in self-renewal capacity of undifferentiated SCs and has the ability to form any cell type of three germ layers of human body.[36,37] The third pluripotency gene is sex-determining region SOX2 which is also a transcription factor and maintains self-renew capacity of undifferentiated SCs.[38]

Although the use of SC has immense medical benefits, their applications in many diseases are still in the research and clinical trial phase and further studies are required for its long-term use in clinical settings. SCs have much more potent regulatory role in immune system. Compared to PRP-based approach, SC therapy can be very promising in treatment of many degenerative diseases where PRP is not suitable. SCs are also been used to treat many dental-related disorders such as regeneration and reconstruction of dental and oromaxillofacial tissues.[39,40] MSCs have shown to support blood and lymphangiogenesis and also shown to act as precursors of endothelial cells and pericytes and promote angiogenesis.[41] MSCs are known to orchestrate wound repair by cellular differentiation, immune modulation and production of growth factors that drive neovascularization and re-epithelialization [].

The promise of stem-cell therapy in regenerative medicine

SC-based therapies are emerging as a powerful tool for treating many degenerative and inflammatory diseases. Apart from differentiating into new tissue that is lost, they also coordinate in repair response. SC can be isolated from patients and can be amenable to autologous transplantation. Treatment with single isolation can provide lifetime repository of cells for the patients. Furthermore, SC can be genetically modified to overexpress crucial genes that can augment wound healing and decrease the formation of scars.[42]

Although SC has added advantage over PRP-based approach in regenerating the damaged tissue, there are certain concerns in using SC for therapies. SC propensity toward self-renewal and differentiation is highly influenced by their local environment making it difficult to interpret how a population of culture expands MSC may behave in vivo. Isolation and characterization of SC are crucial and even the isolated SC may have low survival rates. Culturing of SC without contamination requires highly experienced personnel and sophisticated laboratory settings. The chances of microbial contamination of SC might result in complications, especially in those patients whose immune system is compromised. Careful monitoring and observation of this cell-based therapy are of paramount importance, since evidence has shown that adipose-derived MSCs have lost genetic stability over time and were prone to tumor formation.[43] Based on the specific application, SC should be differentiated into appropriate cell types before they can be clinically used, failure of which may have deleterious effects. Furthermore, SC-based therapies require regular follow-up to monitor regenerated tissue over a period of complete recovery of a patient. In vivo niches, SCs are present under hypoxic conditions and change in oxygen levels can induce oxidative stress, which can influence SC phenotype, proliferation, fate, pluripotency, etc., Therefore, in vitro culture conditions used to study MSCs should be maintained similar to their in vivo niches.[44]

PRP and SC therapy is continuously studied for their regenerative benefit in wound healing, sports medicine and chronic pain treatment. Although their preparation, mechanism and action and efficacy have been shown to be different, studies have shown that both PRP and SC can complement each other and might have an added advantage when used in combination. For example, PRP offers a suitable microenvironment for MSCs to promote proliferation and differentiation and accelerates wound healing capabilities. Conversely, PRP can be a powerful tool to attract cell populations, such as MSCs, a combination of which provides a promising approach for the treatment.[45] Some of the common injuries that are treated using combinational therapy include tendonitis, rotator cuff tears, osteoarthritis, spine conditions, arthritic joints, overuse injuries, inflammation from herniated disc and others.[46,47]

Despite many beneficial effects of PRP in treating clinical conditions and with minimal side effects, the use of PRP as a regenerative medicine is still in its infancy. The major constraint is the limited availability of adequate controlled clinical trials and lack of consensus related to PRP preparation techniques. Nevertheless, the use of PRP-based preparations has shown promising results in some clinical settings, especially in the field of dermatology, dentistry, ophthalmology, orthopedics and others. Future research has to be focused on understanding the molecular mechanisms involved in the PRP-based therapies in tissue regeneration and long-term side effects associated with the use of PRP. Optimum concentration required to attain maximum tissue regeneration response without eliciting the immune response has to be determined. Investigating these key questions would increase the use of PRP-based regenerative medicines in treating acute and chronic ailments rather than using conventional therapies which would include surgeries followed by prolonged supportive therapies.

Although PRP and SC represent a promising treatment for many diseases, large-scale clinical trials using both in vitro and in vivo studies are required to establish the true effectiveness of the treatments. SC-based therapies have shown promising results in clinical settings, and further work should be carried out to optimize the transplantation procedures that ensure functional integration, proliferation, differentiation and migration of transplanted tissue-specific ASCs to repair and replace the damaged tissue and their long-term survival in the tissue niche.

In conclusion, PRP-based therapeutic option could be used as an alternative form of therapy alone or in combination with other conventional treatments. In this regard, it is important to understand the formulations and specific enrichment fractions that could be suitable for particular treatment. Furthermore, research has to focus on standardizing the PRP formulations and have a consensus data from the clinical trials from different research groups for better prognosis and to use as an alternative to conventional therapies.

Nil.

There are no conflicts of interest.

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Stem-cell therapy and platelet-rich plasma in regenerative ...

Meet Dr. Daniel Savarino, DO, RMSK

Dr. Daniel Savarino, DO is a sport and regenerative medicine specialist in Tinton Falls, NJ.

Dr.Savarino, an established and highly skilled physician, has over 10 years of experience in Sports Medicine. He obtained his medical degree at the New York College of Osteopathic Medicine and completed a Family Practice Residency at North Shore LIJ Hospital at Plainview, where he served as Chief Resident in 2007-2008. Before starting Apex Center for Regenerative Medicine, Dr. Savarino worked in one of the busiest orthopedic and sports medicine practices in New York City, where he had extensive training in Musculoskeletal Ultrasound and Ultrasound Guided Injections.Dr. Savarino performs procedures a few other physicians in the country perform, and people travel from different parts of America and from different countries to be treated by him!

Dr. Savarino has demonstrated cutting-edge knowledge and skills needed to provide top care to his patients in the area of Regenerative Medicine, Sports Medicine, and Pain Management. In addition to helping patients avoidunneededsurgery, Dr Savarino has received hundreds of hours of additional training in Non -Surgical Aesthetics & Body Contouring, Age Management Medicine and Bioidentical HormoneReplacement .

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Regenerative Medicine Monmouth County NJ

Combining CRISPR and stem cells to treat diabetes

Decades of clinical data with islet transplants indicate that beta-cell replacement approaches may offer curative benefit to patients with insulin-requiring diabetes. ViaCyte has pioneered the approach of generating pancreatic-lineage cells from stem cells and delivering them safely and efficiently to patients. PEC-Direct, ViaCytes lead product candidate currently being evaluated in the clinic, uses a non-immunoprotective delivery device that permits direct vascularization of the cell therapy. This approach has the potential to deliver durable benefit; however, because the patients immune system will identify these cells as foreign, PEC-Direct will require long-term immunosuppression to avoid rejection. As a result, PEC-Direct is being developed as a therapy for the subset of patients with type 1 diabetes at high risk for complications.

Our gene-editing technology offers the potential to protect the transplanted cells from the patients immune system by ex vivo editing immune-modulatory genes within the stem cell line used to produce the pancreatic-lineage cells. The speed, specificity and multiplexing efficiency of CRISPR/Cas9 make our technology ideally suited to this task. We have established significant expertise in immune-evasive gene editing through our allogeneic CAR-T programs. The combination of ViaCytes stem cell capabilities and our gene-editing capabilities has the potential to enable a beta-cell replacement product that may deliver durable benefit to patients without triggering an immune reaction.

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Regenerative Medicine | CRISPR

DUBLIN, December 22, 2021--(BUSINESS WIRE)--The "Global Regenerative Medicine Market Size, Share & Trends Analysis Report by Product (Cell-based Immunotherapies, Gene Therapies), by Therapeutic Category (Cardiovascular, Oncology), and Segment Forecasts, 2021-2027" report has been added to ResearchAndMarkets.com's offering.

The global regenerative medicine market size is expected to reach USD 57.08 billion by 2027, growing at a CAGR of 11.27% over the forecast period.

Recent advancements in biological therapies have resulted in a gradual shift in preference toward personalized medicinal strategies over the conventional treatment approach. This has resulted in rising R&D activities in the regenerative medicine arena for the development of novel regenerative therapies.

Furthermore, advancements in cell biology, genomics research, and gene-editing technology are anticipated to fuel the growth of the industry. Stem cell-based regenerative therapies are in clinical trials, which may help restore damaged specialized cells in many serious and fatal diseases, such as cancer, Alzheimer's, neurodegenerative diseases, and spinal cord injuries.

For instance, various research institutes have adopted Human Embryonic Stem Cells (hESCs) to develop a treatment for Age-related Macular Degeneration (AMD).

Constant advancements in molecular medicines have led to the development of gene-based therapy, which utilizes targeted delivery of DNA as a medicine to fight against various disorders.

Gene therapy developments are high in oncology due to the rising prevalence and genetically driven pathophysiology of cancer. The steady commercial success of gene therapies is expected to accelerate the growth of the global market over the forecast period.

Regenerative Medicine Market Report Highlights

The number of companies engaged in the development of advanced therapies is continuously increasing over the past few years. This is anticipated to increase the competition among companies to create a specific and efficient pipeline

The therapeutics segment dominated the market in 2020 due to the high usage of primary cell-based therapies along with advances in stem cell and progenitor cell therapies. The implementation of these therapies in dermatological, musculoskeletal, and dental application results in the highest share of this segment

Stem cell and progenitor cell-based therapies are anticipated to witness rapid growth due to high investments in this research space and an increasing number of stem cell banks

With the rise in R&D and clinical trials of regenerative medicines, key players are offering several consulting services leading to lucrative growth of the services segment

The oncology segment is estimated to account for the largest revenue share by 2027 owing to the high prevalence of cancer indications, which drives the demand for better solutions. The presence of a strong pipeline of regenerative medicines for cancer treatment also supplements the segment growth

North America dominated the market in 2020 and is projected to continue its dominance over the forecast period. A significant number of universities and research organizations investigating various stem cell-based approaches for regenerative apposition in the U.S. propels the region's growth

Asia Pacific is projected to witness the fastest CAGR over the forecast period due to the emergence of key players and rapid adoption of cell-based approaches in the healthcare

Key Topics Covered:

Story continues

Market Variables, Trends, & Scope

Market Driver Analysis

Presence of a strong pipeline and a large number of clinical trials

High economic impact of regenerative medicine

Emerging applications of gene therapy in regenerative medicine

Increasing government & private funding to support the development of regenerative medicine

Technological advancements in regenerative medicine (stem cell, tissue engineering, and nanotechnology)

Increase in strategic partnerships to accelerate development & commercialization of regenerative medicines

Rising prevalence of chronic diseases & genetic disorders, degenerative diseases, and bone & joint diseases leading to rise in demand for regenerative treatments

Market Restraint Analysis

High cost of treatment

Regulatory issues pertaining to stem cells, tissues engineering, and regenerative medicines

Market Challenge Analysis

Current challenges of on-market gene therapies

Penetration & Growth Prospect Mapping for Therapeutic Category, 2020

Reimbursement Framework

Reimbursement Framework & Clinical Translation of RM

Reimbursement Framework for RM: Europe

Reimbursement Framework for RM: South Korea

Technology Overview

Autologous Cell Transplantation

Next-Generation Cell-Based Therapies

CAR-T Cell Technologies

Cost Structure Analysis

User Perspective Analysis

Market Influencer Analysis

Consumer Behavior Analysis

Regenerative Medicine Market - SWOT Analysis, by Factor (Political & Legal, Economic, and Technological)

Industry Analysis - Porter's

Regenerative Medicine Market Analysis Tools

Major Deals & Strategic Alliances Analysis

Merger & Acquisition Deals

Collaboration & Partnerships

Business Expansion

Market Entry Strategies

Pharmaceutical and biotechnology companies

Raw material supplier

Contract Service Provider

Distributor

Companion Diagnostics companies:

Case Studies

MACI (Vericel Corporation):

LAVIV (Azficel-T) (Fibrocell Technologies):

Competitive Analysis

Covid-19 Impact Analysis

COVID-19 Impact Analysis

Challenges Analysis

Manufacturing & Supply Challenges

Opportunities analysis

Need For Development Of New Therapies Against SARS-COV-2

T-cell Therapy

Cell Therapy

Gene Therapy

Tissue engineering

Rise In Demand For Supply Chain Management Solutions

Challenges in Manufacturing T-cell Therapies Against COVID-19

Clinical Trial Analysis

Regenerative Medicine Market: Product Business Analysis

Regenerative Medicine Market: Therapeutic Category Business Analysis

Regenerative Medicine Market: Regional Business Analysis

Companies Mentioned

Integra Lifesciences Corporation

Astellas Pharma Inc.

Cook Biotech, Inc.

Bayer AG

Astrazeneca plc

F. Hoffmann-La Roche Ltd.

Pfizer, Inc.

Merck Kgaa

Abbott

Vericel Corporation

Novartis AG

GlaxoSmithKline plc.

Baxter International Inc.

Boehringer Ingelheim GmbH

Amgen Inc.

Cesca Therapeutics Inc. / Thermogenesis Holdings Inc.

U.S Stem Cell, Inc.

Bristol-Myers Squibb Company

Eli Lilly and Company

Nuvasive, Inc.

Organogenesis, Inc.

Mimedx Group, Inc.

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Global Regenerative Medicine Market is Expected to Reach ...

Ageless Regenerative Medical

The most profound influences on your health are the cumulative effects of the choices you make about your diet and lifestyle. Over 80% percent of the signs of aging and disease are caused by your lifestyle behaviors. At Ageless Regenerative Medical in Nashville, Tennessee, our team, led by Dr. Nicholas Sieveking andJan Stanley, RN, MS, focuses on a set of principles that empower you to make those critical lifestyle choices needed to not only look young but also feel young and live longer.

Our mission is to deliver quality care based on compassion and clinical excellence to patients who want to optimize their health and achieve an individualized age management solution. We take an integrative approach to functional and regenerative medicine. Treatments are individualized to meet patients needs and monitored closely to evaluate outcomes accurately and effectively.

Functional medicine evaluates the root causes of disease using a whole systems approach based on genetic, biochemical, and lifestyle factors. Most importantly, it is an individualized partnership that is developed between the patient and practitioner.

Regenerative medicine, an emerging branch of medical science, deals with the functional restoration of tissues or organs for the patient suffering from severe injuries, chronic disease, or for those wishing to improve their overall health. The progress in this field of research has laid the foundation for cell-based therapies of disease which cannot be cured by conventional medicine. The human body can heal itself and fight illnesses through its immune system. Regenerative therapies infuse cells to replace damaged ones as well as initiate growth factors to restore tissues and organ functions.

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Ageless Regenerative Medical: Regenerative Medicine ...