Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells

Schwartz, Robert E.; Reyes, Morayma; Koodie, Lisa; Jiang, Yuehua; Blackstad, Mark; Lund, Troy C.; Lenvik, Todd; Johnson, Sandra K.; Hu, Wei‐Shou; Verfaillie, Catherine M.

doi:10.1172/jci200215182

Cited by 232 publications

(234 citation statements)

References 37 publications

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“…RT-PCR analysis was negative for Oct4 (data not shown), which is a known marker of ES cells and MAPCs (11). MAPCs are a clonal line of multipotent stem cells derived from adult mammalian BM that express CD13, SSEA1 (mouse) or SSEA3 (human), Flk-1, Thy1, and Sca1 (11,21). These results indicated that hBMSCs do not belong to the previously described populations of BM-derived stem cells such as HSCs, MSCs, or MAPCs.…”

Section: Resultsmentioning

confidence: 99%

“…hBMSCs were plated at 3 × 10 4 to 4 × 10 4 cells per square centimeter on 1% Matrigel in 2% FBS, supplemented with 10 -8 M dexamethasone, 25 ng/ml HGF, 10 ng/ml FGF-4, and either 10 mg/ml DMSO or 0.5 mM sodium butyrate (21,23). After 10-14 days of culture, approximately 60% of hBMSCs acquired epithelioid morphology.…”

Section: Resultsmentioning

confidence: 99%

“…To induce neural lineage differentiation, hBMSCs were plated at 4 × 10 4 per square centimeter on BioCoat poly-L-ornithine/laminin-coated dishes (BD) or plastic dishes with 100 ng/ml bFGF, 20 ng/ml EGF, and B27 supplement in DMEM/F12 (3,4) and cultured for up to 14 days. To induce endodermal lineage differentiation, hBMSCs were plated at 3 × 10 4 to 4 × 10 4 cells per square centimeter on 1% Matrigel (BD) in 2% FBS, supplemented with 10 -8 dexamethasone, 25 ng/ml HGF, and 10 ng/ml FGF-4, and cultured for 7 days; thereafter, either 10 mg/ml DMSO or 0.5 mM sodium butyrate was added and cultured for 7 more days (21,23). To induce CMC differentiation of the hBMSCs, hBMSCs were cocultured with freshly isolated NRCMs.…”

Section: Methodsmentioning

confidence: 99%

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Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction

Yoon¹,

Wecker²,

Heyd³

et al. 2005

J. Clin. Invest.

231

142

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We have identified a subpopulation of stem cells within adult human BM, isolated at the single-cell level, that self-renew without loss of multipotency for more than 140 population doublings and exhibit the capacity for differentiation into cells of all 3 germ layers. Based on surface marker expression, these clonally expanded human BM-derived multipotent stem cells (hBMSCs) do not appear to belong to any previously described BM-derived stem cell population. Intramyocardial transplantation of hBMSCs after myocardial infarction resulted in robust engraftment of transplanted cells, which exhibited colocalization with markers of cardiomyocyte (CMC), EC, and smooth muscle cell (SMC) identity, consistent with differentiation of hBMSCs into multiple lineages in vivo. Furthermore, upregulation of paracrine factors including angiogenic cytokines and antiapoptotic factors, and proliferation of host ECs and CMCs, were observed in the hBMSC-transplanted hearts. Coculture of hBMSCs with CMCs, ECs, or SMCs revealed that phenotypic changes of hBMSCs result from both differentiation and fusion. Collectively, the favorable effect of hBMSC transplantation after myocardial infarction appears to be due to augmentation of proliferation and preservation of host myocardial tissues as well as differentiation of hBMSCs for tissue regeneration and repair. To our knowledge, this is the first demonstration that a specific population of multipotent human BM-derived stem cells can induce both therapeutic neovascularization and endogenous and exogenous cardiomyogenesis.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction

Yoon¹,

Wecker²,

Heyd³

et al. 2005

J. Clin. Invest.

231

142

View full text Add to dashboard Cite

show abstract

“…Total lung RNA was isolated from lung tissue or isolated lung fibroblasts as previously described (15). Semiquantitative PCR analysis was done as previously described (18). Real-time PCR was performed on a TaqMan ABI 5700 Sequence Detection System (PE Biosystems, Foster City, California, USA).…”

Section: Introductionmentioning

confidence: 99%

Bone marrow–derived progenitor cells in pulmonary fibrosis

Hashimoto¹,

Jin²,

Liu³

et al. 2004

J. Clin. Invest.

599

266

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“…Recently, cells from extrahepatic sources have been induced to generate mature hepatic cells. Of these, embryonic stem cells (51,53,54), hematopoietic progenitors from bone marrow and cord blood (55)(56)(57)(58), and the so-called multipotent adult progenitor cells (59) are the best studied. Although interlineage transdifferentiation mechanisms may be involved in these phenomena, cell fusions with recipient cells are the cause of others (60,61).…”

Section: Discussionmentioning

confidence: 99%

A population of c-Kitlow(CD45/TER119)– hepatic cell progenitors of 11-day postcoitus mouse embryo liver reconstitutes cell-depleted liver organoids

Minguet¹,

Cortegano²,

Gonzalo³

et al. 2003

J. Clin. Invest.

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Embryo liver morphogenesis takes place after gastrulation and starts with a ventral foregut evagination that reacts to factor signaling from both cardiac mesoderm and septum transversum mesenchyme. Current knowledge of the progenitor stem cell populations involved in this early embryo liver development is scarce. We describe here a population of 11-day postcoitus c-Kit low (CD45/TER119) -liver progenitors that selectively expressed hepatospecific genes and proteins in vivo, was self-maintained in vitro by longterm proliferation, and simultaneously differentiated into functional hepatocytes and bile duct cells. Purified c-Kit low (CD45/TER119) -liver cells cocultured with cell-depleted fetal liver fragments engrafted and repopulated the hepatic cell compartments of the latter organoids, suggesting that they may include the embryonic stem cells responsible for liver development.

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Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells

Cited by 232 publications

References 37 publications

Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction

Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction

Bone marrow–derived progenitor cells in pulmonary fibrosis

A population of c-Kitlow(CD45/TER119)– hepatic cell progenitors of 11-day postcoitus mouse embryo liver reconstitutes cell-depleted liver organoids

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