Human amniotic membrane-derived
mesenchymal cells can form cardiac muscle cells and repair heart damage
A new and non-controversial source of stem cells can
form heart muscle cells and help repair heart damage, according to results of
preliminary lab tests reported in Circulation Research: Journal of the American
Heart Association.
Investigators in Japan used the amniotic membrane to
obtain stem cells called human amniotic membrane-derived mesenchymal cells (hAMCs).
"The amniotic membrane is medical waste that could be
collected and used after delivery," said Shunichiro Miyoshi, M.D., Ph.D., co-author
of the study and assistant professor in the cardiology department and Institute
for Advanced Cardiac Therapeutics at the Keio University School of Medicine in
Tokyo.
In laboratory studies, the hAMCs:
- transformed into heart muscle cells, with 33 percent beating spontaneously.
- improved function of rat hearts 34 percent to 39 percent when injected two
weeks after a heart attack, while untreated hearts continued to decline in function.
- decreased the scarred area of damaged rat hearts 13 percent to 18 percent
when injected after a heart attack.
- survived for more than four weeks in the rat heart without being rejected
by the recipient's immune system, even without immunosuppressive medication.
The ability of hAMCs to convert into heart muscle cells
was far greater than that from mesenchymal cells derived from bone marrow or fat,
Miyoshi said.
That the implanted cells were not rejected is likely
because the amniotic sac is a barrier between a woman and her developing fetus.
To help prevent either of their immune systems from attacking the other as foreign
tissue, the amniotic membrane between them does not produce the proteins that
immune systems use to identify foreign tissue. This means the usual tissue-type
matching (HLA typing) needed prior to transplantation would not be needed if hAMCs
were used. Drugs to suppress the immune system also might not be needed after
transplant.
The findings also suggest that hAMCs can differentiate
into cells of various organs.
"If we had to create a cell bank system to cover every
HLA type, we would need to store a great amount of cells, many of which would
never be used," Miyoshi said. "Because hAMCs do not require such a system, it
would be less expensive and usable for all patients."
Much work remains to be done before testing hAMCs in
humans, said the researchers, who are repeating their experiments in larger animals
and working to boost the number of heart cells generated by the hAMCs.
The investigators "are to be congratulated for their
careful work that has brought forward a cell type that may offer the real potential
for off-the-shelf cardiac myocyte [muscle cell]-based therapy," Marc S. Penn,
M.D., Ph.D., and Maritza E. Mayorga, Ph.D., of the Cleveland Clinic, wrote in
an editorial in Circulation Research.
The lead author is Hiroko Tsuji, M.D. Other co-authors
are: Yukinori Ikegami, M.D.; Naoko Hida; Hironori Asada, M.D.; Ikuko Togashi,
M.D.; Junshi Suzuki, M.D.; Masaki Satake, Ph.D.; Hikaru Nakamizo, M.D.; Mamoru
Tanaka, M.D.; Taisuke Mori, M.D., Ph.D.; Kaoru Segawa, Ph.D.; Nabuhiro Nishiyama,
M.D.; Junko Inoue; Hatsune Makino, Ph.D.; Kenji Miyado, Ph.D.; Satoshi Ogawa,
M.D., Ph.D.; Yasunori Yoshimura, M.D., Ph.D. and Akhiro Umezawa, M.D., Ph.D.
The study was partly funded by Japan's Ministry of Education,
Science and Culture.
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