Context Antibody-based induction therapy plus calcineurin inhibitors (CNIs) reduce acute rejection rates in kidney recipients; however, opportunistic infections and toxic CNI effects remain challenging. Reportedly, mesenchymal stem cells (MSCs) have successfully treated graft-vs-host disease.

Objective To assess autologous MSCs as replacement of antibody induction for patients with end-stage renal disease who undergo ABO-compatible, cross-matchnegative kidney transplants from a living-related donor.

Design, Setting, and Patients One hundred fifty-nine patients were enrolled in this single-site, prospective, open-label, randomized study from February 2008-May 2009, when recruitment was completed.

Intervention Patients were inoculated with marrow-derived autologous MSC (12106/kg) at kidney reperfusion and two weeks later. Fifty-three patients received standard-dose and 52 patients received low-dose CNIs (80% of standard); 51 patients in the control group received antiIL-2 receptor antibodyplusstandard-dose CNIs.

Main Outcome Measures The primary measure was 1-year incidence of acute rejection and renal function (estimated glomerular filtration rate [eGFR]); the secondary measure was patient and graft survival and incidence of adverse events.

Results Patient and graft survival at 13 to 30 months was similar in all groups. After 6 months, 4 of 53 patients (7.5%) in the autologous MSC plus standard-dose CNI group (95% CI, 0.4%-14.7%; P=.04) and 4 of 52 patients (7.7%) in the low-dose group (95% CI, 0.5%-14.9%; P=.046) compared with 11 of 51 controls (21.6%; 95% CI, 10.5%-32.6%) had biopsy-confirmed acute rejection. None of the patients in either autologous MSC group had glucorticoid-resistant rejection, whereas 4 patients (7.8%) in the control showing increased eGFR levels during the first month postsurgery group did (95% CI, 0.6%-15.1%; overall P=.02). Renal function recovered faster among both MSC groups showing increased eGFR levels during the first month after surgery than the control group. Patients receiving standard-dose CNI had a mean difference of 6.2 mL/min per 1.73 m2 (95% CI, 0.4-11.9; P=.04) and those in the low-dose CNI of 10.0 mL/min per 1.73 m2 (95% CI, 3.8-16.2; P=.002). Also, during the 1-year follow-up, combined analysis of MSC-treated groups revealed significantly decreased risk of opportunistic infections than the control group (hazard ratio, 0.42; 95% CI, 0.20-0.85, P=.02)

Conclusion Among patients undergoing renal transplant, the use of autologous MSCs compared with anti-IL-2 receptor antibody induction therapy resulted in lower incidence of acute rejection, decreased risk of opportunistic infection, and better estimated renal function at 1 year.

Trial Registration clinicaltrials.gov Identifier: NCT00658073

See the original post here:
Induction Therapy With Autologous Mesenchymal Stem Cells in Living-Related Kidney Transplants: A Randomized Controlled ...

To: HEALTH, MEDICAL AND NATIONAL EDITORS

MIAMI, March 20, 2012 /PRNewswire-USNewswire/ -- New findings from a transplant study led by scientists from the Diabetes Research Institute (DRI) at the University of Miami Miller School of Medicine and a DRI Federation center at Xiamen University in China showed that mesenchymal stem cells may replace a powerful anti-rejection drug in transplant recipients. The results of this pioneering study involving kidney transplant patients is published in the March 21 issue of the Journal of the American Medical Association (JAMA) and may fundamentally transform the future of clinical transplantation.

(Logo: http://photos.prnewswire.com/prnh/20120126/DC42842LOGO)

Patients undergoing a transplant routinely receive a regimen of immunosuppressive therapy to block the body's immune system from rejecting the donor organ or cells. While these drugs have been shown to improve graft function and minimize rejection episodes, they increase the risk of dangerous side effects, including infections and organ toxicity. To eliminate these adverse effects, scientists at the Diabetes Research Institute and collaborating centers worldwide have been investigating safer methods for preventing transplant rejection and have turned their attention to naturally-occurring cells in the body that have immuno-modulatory properties, like mesenchymal stem cells.

A mesenchymal stem cell (MSC) is a type of cell that can differentiate into bone, cartilage, fat and other body tissues. But MSCs have also been found to have a number of other beneficial therapeutic properties, including their ability to modulate the immune system by inhibiting T-cell proliferation, eliminating graft-vs.-host disease, limiting cytotoxic inflammation and stimulating vascularization, among other benefits.

"This study represents a first, important step towards the definition of cell-based strategies that will one day allow for transplantation without the need for life-long, anti-rejection drugs," said Camillo Ricordi, M.D., director of the University of Miami Diabetes Research Institute and Cell Transplant Center. "The worldwide collaborative strategy of the Diabetes Research Institute Federation and The Cure Alliance has resulted in yet another small step forward in our worldwide cure-focused efforts, indicating safety and efficacy of a stem cell-based strategy towards reducing and eventually eliminating anti-rejection drugs. This is particularly important to the DRI mission, as transplantation without immunosuppression is a major goal in any strategy for transplantation of insulin producing cells and a requirement for becoming a reality for all patients with Type 1 or Type 2 insulin dependent diabetes."

In this recent study, "Induction Therapy with Autologous Mesenchymal Stem Cells in Living-Related Kidney Transplants," patients with end-stage renal disease received infusions of bone-marrow derived autologous mesenchymal stem cells together with either standard-dose or low-dose calcineurin inhibitors (CNI). The control group received an immunosuppression regimen consisting of anti-IL-2 receptor antibody plus standard-dose CNI.

After one year post-transplant, the results of the study indicate that among the patients undergoing a kidney transplant, the use of autologous MSCs compared with the standard immunosuppressive therapy resulted in lower incidence of acute organ rejection, decreased risk of infection and better kidney function.

"We reported on the first 12 months follow-up, which showed no adverse events associated with MSC therapy. We will continue monitoring the patients in the study to assess the long-term effects on kidney transplant function and survival, as well as the safety of MSCs transplantation in this setting. Should long-term safety of MSCs be confirmed, it may be valuable for improving transplantation outcomes while reducing the risks associated with anti-rejection drugs," said Antonello Pileggi, M.D., Ph.D., director of Preclinical Cell Processing and Translational Models Program at the Cell Transplant Center of the DRI.

"This collaboration was part of the ongoing global efforts of The Diabetes Research Institute Federation and of The Cure Focus Research Alliance. The opportunity to contribute these results obtained through the combined team efforts of Affiliated Fuzhou General Hospital of Xiamen University and DRI to a journal as high impact as JAMA represents an important achievement for the China-USA Collaborative Human Cell Transplant Program at the Cell Transplant Center of DRI," said Xiumin Xu, M.S., director of the China-US Collaborative Human Cell Transplant Program at the Diabetes Research Institute.

The rest is here:
Collaborative Study from the Diabetes Research Institute Federation and The Cure Alliance Shows that Stem Cells Can ...

Newswise CHICAGO Among patients with end-stage renal disease undergoing living-related kidney transplants, the use of bone-marrow derived mesenchymal (cells that can differentiate into a variety of cell types) stem cells instead of antibody induction therapy resulted in a lower incidence of acute rejection, decreased risk of opportunistic infection, and better estimated kidney function at 1 year, according to a study in the March 21 issue of JAMA.

Induction therapy, routinely implemented in organ transplant procedures, consists of use of biologic agents to block early immune activation. New induction immunosuppressive protocols with increased efficacy and minimal adverse effects are desirable. "Antibody-based induction therapy plus calcineurin inhibitors (CNIs) reduce acute rejection rates in kidney recipients; however, opportunistic infections and toxic CNI effects remain challenging. Reportedly, mesenchymal stem cells (MSCs) have successfully treated graft-vs.-host disease," according to background information in the article.

Jianming Tan, M.D., Ph.D., of Xiamen University, Fuzhou, China and colleagues examined the effect of autologous (derived from the same individual) MSC infusion as an alternative to anti-IL-2 receptor antibody for induction therapy in adults undergoing living-related donor kidney transplants. The randomized study included 159 patients. Patients were inoculated with marrow-derived autologous MSC at kidney reperfusion and two weeks later. Fifty-three patients received standard-dose and 52 patients received low-dose CNIs (80 percent of standard); 51 patients in the control group received anti-IL-2 receptor antibody plus standard-dose CNIs.

Patient and graft survival at 13 to 30 months was similar in all groups. The researchers found that after 6 months, 4 of 53 patients (7.5 percent) in the autologous MSC plus standard-dose CNI group and 4 of 52 patients (7.7 percent) in the low-dose group compared with 11 of 51 controls (21.6 percent) had biopsy-confirmed acute rejection. Renal function recovered faster among both MSC groups showing increased estimated glomerular filtration rate (eGFR; a measure of kidney function) levels during the first month after surgery than the control group.

The authors also found that during the 1-year follow-up, combined analysis of MSC-treated groups revealed significantly decreased risk of opportunistic infections than the control group.

"In our prospective randomized trial on a large patient population, autologous MSCs could replace anti-IL-2 receptor-induction therapy in living-related donor kidney transplants. Recipients of autologous MSCs showed lower frequency of biopsy-confirmed acute rejection in the first 6 months than the control group," the researchers write.

"Extended monitoring of study participants will allow assessment of the long-term effects of autologous MSCs on renal allograft function, survival, and safety."

###

(JAMA. 2012;307[11]:1169-1177. Available pre-embargo to the media at http://www.jamamedia.org)

Editor's Note: This study was supported in part by grants from the Key Science Research Project and the Key Laboratory, both of Fujian Province, China. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Read more from the original source:
Use of Stem Cells for Adults Receiving Related Donor Kidney Transplants Appears to Improve Outcomes

SILVER SPRING, MD.--(BUSINESS WIRE)--

Nuvilex, Inc. (OTCQB:NVLX), an emerging biotechnology provider of cell and gene therapy solutions through its acquisition of the SG Austria assets, today discussed the value of encapsulation, freezing, storage, survivability and localization of human stem cells once implanted using the proprietary Cell-in-a-Box technology.

The encapsulation of human stem cells is enabled by the Cell-in-a-Box technology, which can then be frozen, stored and later implanted into target tissues. The benefits of encapsulation are several: first, the process allows for freezing of stem cells for long-term storage without appreciably affecting viability. Second, encapsulation protects the stem cells from stress factors caused by direct aeration and sheer forces associated with bioreactors. Third, Cell-in-a-Boxencapsulated stem cells are held in place at the site of implantation, maximizing their potential efficacy as they have the potential to stimulate growth of surrounding new, healthy tissue. Finally, encapsulated cells may prevent any potential side effects associated with direct injection since they remain localized to the area of treatment when encapsulated.

Dr. Robert Ryan, Chief Executive Officer of Nuvilex, commented, "For many years it was assumed stem cells existed only to replace cells that had died or were damaged. Recent studies suggest factors stem cells secrete provide signals to surrounding tissue that can stimulate regeneration. The potential therefore, is that if stem cells can be maintained at a particular site where damaged, removed or non-functional tissue was through some sort of holding mechanism, this may aid in a positive growth response in that tissue. In addition, the stem cells themselves have the potential to undergo development into the appropriate cell type at that location, potentially creating miniature organs. The Cell-in-a-Boxtechnology is designed specifically for those purposes. Thus, encapsulated stem cells would be implanted and remain in place, ultimately being able to serve a broad number of medical applications entirely dependent on where in the body they are placed."

About Nuvilex

Nuvilex, Inc. (OTCQB:NVLX) is an emerging international biotechnology provider of live clinically useful, therapeutically valuable, encapsulated cells, as well as services for encapsulating live cells for the research and medical communities. Through substantial effort, the aspects of our corporate activities alone and in concert with SG Austria continue to move toward agreement completion and ultimately a strong future together. Our company's ultimate clinical offerings will include cancer, diabetes and other treatments using the company's industry-leading cell and gene therapy expertise and cutting edge, live-cell encapsulation technology.

Safe Harbor Statement

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 involving risks and uncertainties, including product demand, market competition, and Nuvilex's ability to meet current or future plans which may cause actual results, events, and performances, expressed or implied, to vary and/or differ from those contemplated or predicted. Investors should study and understand all risks before making an investment decision. Readers are recommended not to place undue reliance on forward-looking statements or information. Nuvilex is not obliged to publicly release revisions to any forward-looking statement, to reflect events or circumstances afterward, or to disclose unanticipated occurrences, except as required under applicable laws.

View post:
Cell-In-A-Box Encapsulation Technology Creates Extensive Applications Within The Stem Cell Arena

MCKINNEY (CBSDFW.COM) - If you have ever dealt with back pain, then you know how quickly it can take over your life. But some North Texans are discovering that tiny cells in their own bodies could be key to long-lasting relief.

A simple walk on a beautiful day is not something that Kim Ferracioli takes for granted, as the McKinney resident has been dealing with debilitating back pain for years due to a bad disk in her lower spine. It was so painful, she said. Everytime I would stand up or sit too long, it was just a horrible pinching feeling.

When steroid injections, physical therapy and a minimally-invasive surgery actually made the pain worse, Ferracioli decided to try a new therapy that is revolutionizing the way that doctors treat spinal injuries.

Were using your stem cells, which decreases the rate for complications, explained Dr. Rob Dickerman, a neurosurgeon and one of a few doctors in the country using a patients own stem cells to actually grow new bones from scratch. We can remove a disk and put them between the bones of the spine, and itll stimulate a fusion.

Dickerman removes stem cells from a patients hip and places them in a disk-like carrier. Once implanted into the patients spine, within three months, the stem cells begin to grow into new bone where the damaged disk was removed.

There was an automatic difference, said Ferracioli about the procedure. I could get up out of chairs. I didnt need the cane anymore.

Dickerman said that the success of these procedures are just the first steps for stem cell use in the spine. He hopes that they will soon be able to treat more serious injuries. If we can tweak these cells, Dickerman explained, to make it beneficial to these patients that for the most part have irreparable injuries, that would just be a huge advance in science.

Research is already underway in several labs around the world, transplanting a patients own stem cells to repair spinal cord injuries and even traumatic brain injuries. Dickerman hopes to see these treatments hit the mainstream within the next few years.

In the meantime, Ferracioli said that this new procedure is the only thing that gave her life back. I had to literally pull this back leg up the stairs, Ferracioli recalled. Now, I can just go no pain!

Also Check Out:

View post:
Stem Cells Could Be Key To Back Pain Relief