Abstract
Previously, we reported that a cell population derived from human fetal bone marrow (BM), termed here Flk1+CD34− postembryonic pluripotent stem cells (PPSCs) that have the characteristics of mesenchymal stem cells (MSCs), could differentiate into ectodermal, endodermal and mesodermal cell types at the single cell level in vitro, and that these cells could also differentiate into the epithelium of liver, lung, gut, as well as the hematopoietic and endothelial lineages after transplantion into irradiated non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. In this study, we further isolated pluripotent stem cells from human fetal heart, liver, muscle, lung, derma, kidney, and fat and then analyzed the characteristics and function of these stem cells. It was found that the phenotype of the culture-expanded pluripotent stem cells from different fetal tissues was similar to BM-derived Flk1+CD34− PPSCs, i.e. Flk1 and CD44 positive, GlyA, CD34, CD45, class I-HLA and HLA-DR negative. Morphologically, these cells were fibroblast-like and the doubling time was about 30 h. More importantly, culture-expanded pluripotent stem cells from all these fetal tissues were able to differentiate into cells with morphologic and phenotypic characteristics of adipocytes, osteocytes, neurons, glial cells and hepatocytes. These pluripotent stem cells with characteristics similar to fetal BM-derived Flk1+CD34− PPSCs can be selected and cultured from tissues other than the BM. This phenomenon may help explain the “stem cell plasticity” found in multiple human tissues. In addition, as fetal BM-derived Flk1 + CD34− PPSCs, these pluripotent stem cells from different fetal tissues had the capacity for self-renewal and multi-lineage differentiation even after being expanded for more than 40 population doublings in vitro. Thus, they may be an ideal source of stem cells for treatment of inherited or degenerative diseases.
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References
Fang B, Liao L, Shi M, Yang S, Zhao R C. Identification of Flk1+CD34− pluripotent stem cells derived from human fetal bone marrow. J Lab Clin Med, 2004, 143(4):230–240
Guo H, Fang B, Liao L, Zhao Z, Liu J, Chen H, Hsu S H, Cui Q, Zhao R C. Hemangioblastic characteristics of fetal bone marrow-derived Flk1(+)CD31−CD34(−) cells. Exp Hematol, 2003, 31(7):650–658
Fang B, Shi M, Liao L, Yang S, Liu Y, Zhao R C. Multiorgan engraftment and multilineage differentiation by human fetal bone marrow Flk1+/CD31−/CD34− Progenitors. J Hematother Stem Cell Res, 2003, 12(6):603–613
Hu Y, Liao L, Wang Q, Ma L, Ma G, Jiang X, Zhao R C. Isolation and identification of mesenchymal stem cells from human fetal pancreas. J Lab Clin Med, 2003, 141(5):342–349
Gussoni E, Soneoka Y, Strickland C D, Buzney E A, Khan M K, Flint A F, Kunkel L M, Mulligan R C. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature, 1999, 23401(6751):390–394
Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner J M. Isolation of putative progenitor endothelial cells for angiogenesis. Science, 1997, 275(5302):964–967
Lin Y, Weisdorf D J, Solovey A, Hebbel R P. Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest, 2000, 105(1):71–77
Orlic D, Kajstura J, Chimenti S, Limana F, Jakoniuk I, Quaini F, Nadal-Ginard B, Bodine D M, Leri A, Anversa P. Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci U S A, 2001, 98(18):10344–10349
Goodell M A, Jackson K A, Majka S M, Mi T, Wang H, Pocius J, Hartley C J, Majesky M W, Entman M L, Michael L H, Hirschi K K. Stem cell plasticity in muscle and bone marrow. Ann N Y Acad Sci, 2001, 938:208–218; discussion 218–220
Theise N D, Badve S, Saxena R, Henegariu O, Sell S, Crawford J M, Krause D S. Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation. Hepatology, 2000, 31(1):235–240
Lagasse E, Connors H, Al-Dhalimy M, Reitsma M, Dohse M, Osborne L, Wang X, Finegold M, Weissman I L, Grompe M. Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med, 2000, 6(11):1229–1234
Noort W A, Kruisselbrink A B, in’t Anker P S, Kruger M, van Bezooijen R L, de Paus R A, Heemskerk M H, Lowik C W, Falkenburg J H, Willemze R, Fibbe W E. Mesenchymal stem cells promote engraftment of human umbilical cord blood-derived CD34(+) cells in NOD/SCID mice. Exp Hematol, 2002, 30(8):870–878
Campagnoli C, Roberts I A, Kumar S, Bennett P R, Bellantuono I, Fisk N M. Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood, 2001, 98(8):2396–2402
Zuk P A, Zhu M, Mizuno H, Huang J, Futrell J W, Katz A J, Benhaim P, Lorenz H P, Hedrick M H. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng, 2001, 7(2):211–228
de Bari C, Dell’Accio F, Tylzanowski P, Luyten F P. Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis Rheum, 2001, 44(8):1928–1942
Erices A, Conget P, Minguell J J. Mesenchymal progenitor cells in human umbilical cord blood. Br J Haematol, 2000, 109(1):235–242
Clarke D L, Johansson C B, Wilbertz J, Veress B, Nilsson E, Karlstrom H, Lendahl U, Frisen J. Generalized potential of adult neural stem cells. Science, 2000, 288(5471):1660–1663
Watt F M, Hogan B L. Out of Eden: stem cells and their niches. Science, 2000, 287(5457):1427–1430
McKay R. Stem cells—hype and hope. Nature, 2000, 406(6794):361–364
Schwartz R E, Reyes M, Koodie L, Jiang Y, Blackstad M, Lund T, Lenvik T, Johnson S, Hu W S, Verfaillie C M. Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. J Clin Invest, 2002, 109(10):1291–1302
Kakinuma S, Tanaka Y, Chinzei R, Watanabe M, Shimizu-Saito K, Hara Y, Teramoto K, Arii S, Sato C, Takase K, Yasumizu T, Teraoka H. Human umbilical cord blood as a source of transplantable hepatic progenitor cells. Stem Cells, 2003, 21(2):217–227
Jiang Y, Jahagirdar B N, Reinhardt R L, Schwartz R E, Keene C D, Ortiz-Gonzalez X R, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low W C, Largaespada D A, Verfaillie C M. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature, 2002, 418(6893):41–49
Terada N, Hamazaki T, Oka M, Hoki M, Mastalerz D M, Nakano Y, Meyer E M, Morel L, Petersen B E, Scott E W. Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature, 2002, 416(6880):542–545
Ying Q L, Nichols J, Evans E P, Smith A G. Changing potency by spontaneous fusion. Nature, 2002, 416(6880):545–548
Spees J L, Olson S D, Ylostalo J, Lynch P J, Smith J, Perry A, Peister A, Wang M Y, Prockop D J. Differentiation, cell fusion, and nuclear fusion during ex vivo repair of epithelium by human adult stem cells from bone marrow stroma. Proc Natl Acad Sci USA, 2003, 100(5):2397–2402
Wang X, Willenbring H, Akkari Y, Torimaru Y, Foster M, Al-Dhalimy M, Lagasse E, Finegold M, Olson S, Grompe M. Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature, 2003, 422(6934):897–901
Vassilopoulos G, Wang P R, Russell D W. Transplanted bone marrow regenerates liver by cell fusion. Nature, 2003, 422(6934):901–904
Galli R, Borello U, Gritti A, Minasi M G, Bjornson C, Coletta M, Mora M, de Angelis M G, Fiocco R, Cossu G, Vescovi A L. Skeletal myogenic potential of human and mouse neural stem cells. Natl Neurosci, 2000, 3(10):986–991
Rietze R L, Valcanis H, Brooker G F, Thomas T, Voss A K, Bartlett P F. Purification of a pluripotent neural stem cell from the adult mouse brain. Nature, 2001, 412(6848):736–739
Ianus A, Holz G G, Theise N D, Hussain M A. In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. J Clin Invest, 2003, 111(6):843–850
Reyes M, Lund T, Lenvik T, Aguiar D, Koodie L, Verfaillie C M. Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells. Blood, 2001, 98(9):2615–2625
Reyes M, Dudek A, Jahagirdar B, Koodie L, Marker P H, Verfaillie C M. Origin of endothelial progenitors in human postnatal bone marrow. J Clin Invest, 2002, 109(3):337–346
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Fang, B., Song, Y., Zhao, C. et al. Pluripotent stem cells exhibiting similar characteristics can be isolated from human fetal bone marrow, heart, liver, muscle, lung, derma, kidney, and fat. Front. Med. China 1, 185–191 (2007). https://doi.org/10.1007/s11684-007-0035-1
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DOI: https://doi.org/10.1007/s11684-007-0035-1