By Philip C. Tubeza

Health Secretary Enrique Ona said that the Department of Health would come out in the coming weeks with the rules to regulate stem cell therapy in the country. INQUIRER FILE PHOTO

MANILA, PhilippinesHealth buffs may abhor body fat but it is actually a good source for stem cells that can be used to help treat diseases ranging from athritis, diabetes, or even HIV/AIDS in the future, according to a stem cell expert.

Speaking at the first national convention of the Philippine Society for Stem Cell Medicine, Vasilis Paspaliaris, a stem cell expert from Greece, said body fat or adipose tissues have been proven to be rich sources of mesenchyme stem cells, used for regenerative medicine.

Why fat? Whats the interest in fat? Theres a lot more mesenchyme stem cells in adipose tissue, Paspaliaris said during the convention at the Manila Hotel.

Many of you cosmetic surgeons know that fat has been used as a filler for breast enhancements. Everyone knew there was a therapeutic use for fat. And plastic surgeons were quite aware of it. They have seen its rejuvenative effects, he added.

He said that while mesenchyme tissues could also be found in the skin and the kidneys, there is 10,000 times more mesancyme stem cells in adipose tissue.

And what is a big deal in adipose tissue is that (its) easily accessible with a minimal invasive procedure. More importantly, we can take a little amount of fat and we already have enough numbers of cells that we can take back straight to our patients, he added.

However, Paspaliaris said that the fat person would not necessarily have more mesenchyme stem cells than someone thinner.

The bigger you are does not mean that you have more stem cells. It just means you have more lipids (or stored energy), he added.

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Body fat good source of stem cells, say doctors

SAN DIEGO Researchers at the University of California, San Diego School of Medicine have discovered that hard-to-reach, drug-resistant leukemia stem cells (LSCs) that overexpress multiple pro-survival protein forms are sensitive and thus vulnerable to a novel cancer stem cell-targeting drug currently under development.

The findings, published in today's (Jan. 17) online issue of Cell Stem Cell, open the possibility that diseases like chronic myeloid leukemia (CML) and some solid tumor cancers might in combination with other therapies be more effectively treated with this drug, and with a lower chance of relapse.

Led by principal investigator Catriona H. M. Jamieson, M.D., Ph.D., associate professor of medicine and director of stem cell research at UC San Diego Moores Cancer Center, the researchers found that a compound called sabutoclax appears to selectively target LSCs that express particular protein isoforms through alternatively splicing, a fundamental process in which a gene is able to code for multiple proteins.

Jamieson and colleagues found that alternative splicing of BCL2 genes, which code for proteins involved in apoptosis or programmed cell death, specifically promoted malignant transformation of dormant white blood cell precursors into "blast crisis" LSCs. The blast crisis is the final phase of CML when overabundant, abnormal white blood cells crowd out healthy cells, causing serious dysfunction.

Of clinical importance, they noted that sabutoclax, which suppresses all BCL2 anti-apoptotic proteins, renders these marrow-dwelling blast crisis LSCs sensitive and more susceptible to TKI-based therapeutics at doses that do not harm normal progenitor cells.

"Our findings show that pan-BCL2 inhibition will be critical for the eradication of cancer stem cells in CML and that there is an essential link between cancer stem cell dormancy, pro-survival BCL2 isoform expression and therapeutic resistance," Jamieson said. "By using a novel pan-BCL2 inhibitor, we may be able to prevent therapeutic resistance by sensitizing malignant stem cell clones to TKIs."

The findings may have implications for treating solid tumor cancers, such as colon, prostate, breast, and brain cancers, noted Daniel J. Goff, the study's first author. "With many of these tumor types being shown to harbor cancer stem cells, it raises the question of whether BCL2 family expression as well as isoform-switching may be crucial for the maintenance of cancer stem cells in these diseases as well," he said. "If so, they may also be candidates for treatment with a BCL2 inhibitor like sabutoclax."

Co-authors are Angela Court Recart, Anil Sadarangani, Heather Leu, Janine Low-Marchelli, Wenxue Ma, Alice Y. Shih, Ifat Geron, Minya Pu, Lei Bao, Ryan Chuang, Larisa Balaian, Peggy Wentworth, Kristen M. Smith, Christina A.M. Jamieson, Sheldon R. Rorris and Karen Messer, UC San Diego Department of Medicine and UC San Diego Moores Cancer Center; Hye-Jung Chun and Marco Marra, Michael Smith Genome Sciences Center, Vancouver, B.C., Canada; Christian L. Barrett and Kelly A. Frazer, UC San Diego Department of Pediatrics; Maryla Krajewska, Jun Wei, Dayong Zhai, Maurizio Pellecchia and John C. Reed, Sanford-Burnham Medical Research Institute; Jason Gotlib, Stanford Medical Center; Mark Minden, Princess Margaret Hospital, Toronto, Canada; Giovanni Martinelli, Institute of Hematology and Medical Oncology, University of Bologna, Italy; Jessica Rusert and Lawrence S.B. Goldstein, UC San Diego Department of Cellular and Molecular Medicine and Howard Hughes Medical Institute; Kim-Hien Dao, Oregon Health and Science University, Portland; Kamran Shazand and Thomas J. Hudson, Ontario Institute for Cancer Research, Toronto, Canada.

Funding for this research was provided by a California Institute for Regenerative Medicine (CIRM) early Translational II grant (TR2-1789), a CIRM HALT leukemia disease team grant (DR1-01430), the UCSD CIRM Training Grant (TG2-01154), the Ratner Family Foundation, the National Cancer Institute (CA-55164), the National Institutes of Health (CA-149668), the Ontario Institute for Cancer Research, Genome Canada, Ontario Genomics Institute and the Canadian Institute of Health Research.

Excerpt from:
Drug targets leukemia stem cells

Mouse nervous-system cells (green), hijacked and turned by leprosy bacteria into stem cells, attack muscle fibre (red).

Rambukkana Lab members

Leprosy bacteria can reprogram cells to revert to a stem-cell-like state, able to mature into different cell types, researchers report today in Cell1.

The scientists stumbled on the discovery while researching the way leprosy spreads around the body. The mechanism of the hijacking is unclear, but reproducing it could lead to new stem-cell-based therapeutic strategies.

The initial target of the leprosy bacterium Mycobacterium leprae is Schwann cells, which are part of the peripheral nervous system. Like rubber around an electric wire, the cells wrap around nerves to insulate the electric signals passing through.

The researchers isolated Schwann cells from mice and infected them with M. leprae. The bacteria reprogrammed the cells into a stem-like state, turning off genes associated with mature Schwann cells and turning on embryonic or developmental ones.

The bacteria appeared to trigger Schwann cells' plasticity, the ability to revert to an immature state and turn into new types of cells. (Healthy Schwann cells do so to help nerves recover and regenerate after an injury.)

This is a very sophisticated mechanism it seems that the bacterium knows the mechanistic interaction of the Schwann cell better than we do, says Anura Rambukkana, a regeneration biologist at the University of Edinburgh, UK, who led the study.

Once reprogrammed, the stem cells are able to migrate to different body areas, and the bacteria ride along. When the infected cells reach another tissue, such as skeletal muscle, they integrate with that tissue's cells, spreading the bacteria. The infected stem cells were also found to attract immune cells by secreting proteins called chemokines allowing the bacteria to hitch a ride on these cells as well.

The researchers do not know what triggers the reprogramming event, but they suspect that the mechanism could exist in other infectious diseases.

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Leprosy bug turns adult cells into stem cells

Newswise Researchers at the University of California, San Diego School of Medicine have discovered that hard-to-reach, drug-resistant leukemia stem cells (LSCs) that overexpress multiple pro-survival protein forms are sensitive and thus vulnerable to a novel cancer stem cell-targeting drug currently under development.

The findings, published in the January 17 online issue of Cell Stem Cell, open the possibility that diseases like chronic myeloid leukemia (CML) and some solid tumor cancers might in combination with other therapies be more effectively treated with this drug, and with a lower chance of relapse.

Led by principal investigator Catriona H. M. Jamieson, MD, PhD, associate professor of medicine and director of stem cell research at UC San Diego Moores Cancer Center, the researchers found that a compound called sabutoclax appears to selectively target LSCs that express particular protein isoforms through alternatively splicing, a fundamental process in which a gene is able to code for multiple proteins.

An emerging class of drugs called tyrosine kinase inhibitors (TKI) such as imitinib (Gleevec), gifitinib (Iressa) and sunitinib (Sutent) has become a popular anti-cancer treatment. However, current TKIs are not 100 percent effective. In cases of CML, for example, some LSCs tucked protectively within bone marrow elude destruction, develop resistance to therapy, self-renew and eventually cause the leukemia to dramatically return.

Jamieson and colleagues found that alternative splicing of BCL2 genes, which code for proteins involved in apoptosis or programmed cell death, specifically promoted malignant transformation of dormant white blood cell precursors into blast crisis LSCs. The blast crisis is the final phase of CML when overabundant, abnormal white blood cells crowd out healthy cells, causing serious dysfunction.

Of clinical importance, they noted that sabutoclax, which suppresses all BCL2 anti-apoptotic proteins, renders these marrow-dwelling blast crisis LSCs sensitive and more susceptible to TKI-based therapeutics at doses that do not harm normal progenitor cells.

Our findings show that pan-BCL2 inhibition will be critical for the eradication of cancer stem cells in CML and that there is an essential link between cancer stem cell dormancy, pro-survival BCL2 isoform expression and therapeutic resistance, Jamieson said. By using a novel pan-BCL2 inhibitor, we may be able to prevent therapeutic resistance by sensitizing malignant stem cell clones to TKIs.

The findings may have implications for treating solid tumor cancers, such as colon, prostate, breast, and brain cancers, noted Daniel J. Goff, the studys first author. With many of these tumor types being shown to harbor cancer stem cells, it raises the question of whether BCL2 family expression as well as isoform-switching may be crucial for the maintenance of cancer stem cells in these diseases as well, he said. If so, they may also be candidates for treatment with a BCL2 inhibitor like sabutoclax.

Co-authors are Angela Court Recart, Anil Sadarangani, Heather Leu, Janine Low-Marchelli, Wenxue Ma, Alice Y. Shih, Ifat Geron, Minya Pu, Lei Bao, Ryan Chuang, Larisa Balaian, Peggy Wentworth, Kristen M. Smith, Christina A.M. Jamieson, Sheldon R. Rorris and Karen Messer, UCSD Department of Medicine and UCSD Moores Cancer Center; Hye-Jung Chun and Marco Marra, Michael Smith Genome Sciences Center, Vancouver, BC, Canada; Christian L. Barrett and Kelly A. Frazer, UCSD Department of Pediatrics; Maryla Krajewska, Jun Wei, Dayong Zhai, Maurizio Pellecchia and John C. Reed, Sanford-Burnham Medical Research Institute; Jason Gotlib, Stanford Medical Center; Mark Minden, Princess Margaret Hospital, Toronto, Canada; Giovanni Martinelli, Institute of Hematology and Medical Oncology, University of Bologna, Italy; Jessica Rusert and Lawrence S.B. Goldstein, UCSD Department of Cellular and Molecular Medicine and Howard Hughes Medical Institute; Kim-Hien Dao, Oregon Health and Science University, Portland; Kamran Shazand and Thomas J. Hudson, Ontario Institute for Cancer Research, Toronto, Canada.

Funding for this research was provided by a California Institute for Regenerative Medicine (CIRM) early Translational II grant (TR2-1789), a CIRM HALT leukemia disease team grant (DR1-01430), the UCSD CIRM Training Grant (TG2-01154), the Ratner Family Foundation, the National Cancer Institute (CA-55164), the National Institutes of Health (CA-149668), the Ontario Institute for Cancer Research, Genome Canada, Ontario Genomics Institute and the Canadian Institute of Health Research.

See more here:
Drug Targets Hard-to-Reach Leukemia Stem Cells Responsible for Relapses