Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Yoon YS

PROVIDER: S-EPMC546424 | biostudies-literature | 2005 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Yoon Young-sup YS Wecker Andrea A Heyd Lindsay L Park Jong-Seon JS Tkebuchava Tengiz T Kusano Kengo K Hanley Allison A Scadova Heather H Qin Gangjian G Cha Dong-Hyun DH Johnson Kirby L KL Aikawa Ryuichi R Asahara Takayuki T Losordo Douglas W DW

The Journal of clinical investigation 20050201 2

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 hB ...[more]

PMID: 15690083

Similar Datasets

Project description:Adult bone marrow-derived very small embryonic-like stem cells (VSEL-SCs) exhibit a Sca-1(+)/Lin(-)/CD45(-) phenotype and can differentiate into various cell types, including cardiomyocytes and endothelial cells. We have previously reported that transplantation of a small number (1 × 10(6)) of freshly isolated, non-expanded VSEL-SCs into infarcted mouse hearts resulted in improved left ventricular (LV) function and anatomy. Clinical translation, however, will require large numbers of cells. Because the frequency of VSEL-SCs in the marrow is very low, we examined whether VSEL-SCs can be expanded in culture without loss of therapeutic efficacy. Mice underwent a 30 min. coronary occlusion followed by reperfusion and, 48 hrs later, received an intramyocardial injection of vehicle (group I, n = 11), 1 × 10(5) enhanced green fluorescent protein (EGFP)-labelled expanded untreated VSEL-SCs (group II, n = 7), or 1 × 10(5) EGFP-labelled expanded VSEL-SCs pre-incubated in a cardiogenic medium (group III, n = 8). At 35 days after myocardial infarction (MI), mice treated with pre-incubated VSEL-SCs exhibited better global and regional LV systolic function and less LV hypertrophy compared with vehicle-treated controls. In contrast, transplantation of expanded but untreated VSEL-SCs did not produce appreciable reparative benefits. Scattered EGFP(+) cells expressing α-sarcomeric actin, platelet endothelial cell adhesion molecule (PECAM)-1, or von Willebrand factor were present in VSEL-SC-treated mice, but their numbers were very small. No tumour formation was observed. We conclude that VSEL-SCs expanded in culture retain the ability to alleviate LV dysfunction and remodelling after a reperfused MI provided that they are exposed to a combination of cardiomyogenic growth factors and cytokines prior to transplantation. Counter intuitively, the mechanism whereby such pre-incubation confers therapeutic efficacy does not involve differentiation into new cardiac cells. These results support the potential therapeutic utility of VSEL-SCs for cardiac repair.

Project description:The study examined the long-term outcome of cardiac stem cell transplantation in hearts with postinfarction left ventricular (LV) remodeling. Myocardial infarction (MI) was created by ligating the first and second diagonal branches of the left anterior descending coronary artery in miniature swine. Intramyocardial injections of 50 million LacZ-labeled bone marrow-derived multipotent progenitor cells (MPC) were performed in the periscar region (Cell, n = 7) immediately after MI, whereas, in control animals (Cont, n = 7), saline was injected. Functional outcome was assessed monthly for 4 mo with MRI and (31)P-magnetic resonance spectroscopy. Engraftment was studied on histology, and gene chip (Affymetrix) array analysis was used to study differential expression of genes in the two groups. MPC treatment resulted in improvement of ejection fraction as early as 10 days after MI (Cell, 43.4 +/- 5.1% vs. Cont, 32.2 +/- 5.5%; P < 0.05). This improvement was seen each month and persisted to 4 mo (Cell, 51.2 +/- 4.8% vs. Cont, 35.7 +/- 5.0%; P < 0.05). PCr-to-ATP ratio (PCr/ATP) improved with MPC transplantation, which was most pronounced at high cardiac work states (subendocardial PCr/ATP was 1.70 +/- 0.10 vs. 1.34 +/- 0.14, P < 0.05). There was no significant difference in scar size (scar/LV area * 100) at 10 days postinfarction. However, at 4 mo, there was a significant decrease in scar size in the Cell group (Cell, 4.6 +/- 1.0% vs. Cont, 8.6 +/- 2.4%; P < 0.05). No significant engraftment of MPC was observed. MPC transplantation was associated with a downregulation of mitochondrial oxidative enzymes and increased levels of myocyte enhancer factor 2a and zinc finger protein 91. In conclusion, MPC transplantation leads to long-term functional and bioenergetic improvement in a porcine model of postinfarction LV remodeling, despite no significant engraftment of stem cells in the heart. MPC transplantation reduces regional wall stresses and infarct size and mitigates the adverse effects of LV remodeling, as seen by a reduction in LV hypertrophy and LV dilatation, and is associated with differential expression of genes relating to metabolism and apoptosis.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets