Ex vivo differentiation of human adult bone marrow stem cells into cardiomyocyte-like cells

Shim, Winston; Jiang, Shengming; Wong, Philip; Tan, Jennifer K.; Chua, Yeow Leng; Tan, Yong Seng; Sin, Yoong Kong; Lim, Chong Hee; Chua, Terrance; Teh, Ming; Liu, Te Chih; Sim, Eugene K.W.

doi:10.1016/j.bbrc.2004.09.087

Cited by 175 publications

(121 citation statements)

References 31 publications

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“…The in vitro assessment of the differentiation potential of MSCs has been mainly monitored in cultures containing either MSCs alone treated with 5-azacytidine or with a cocktail of defined growth factors [Shim et al, 2004;Xaymardan et al, 2004]. Cell treatment with 5-azacytidine has a long scientific history, as it has been at first proposed to induce differentiation in several cell lines, mainly in an attempt to reduce the aggressivity of transformed cells.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, regarding heart repair, they have been shown to potentially originate both endothelial vascular cells and cardiomyocytes. Among the different strategies proposed to promote in vitro cardiac differentiation of MSCs, chronic exposure to 5-azacytidine has been amply tested [reviewed by Leri et al, 2005], as well as stimulation by exogenous cytokines and growth factors [Xaymardan et al, 2004, Shim et al, 2004, and coculture with neonatal cardiac cell [Lagostena et al, 2005] or immortalized cardiac cell lines [Rangappa et al, 2003]. Cocultures between MSCs and adult cardiomyocytes were performed mainly to show functional connection between the two cell types [Valiunas et al, 2004].…”

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confidence: 99%

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Limited plasticity of mesenchymal stem cells cocultured with adult cardiomyocytes

Gallo¹,

Ramella²,

Alloatti³

et al. 2006

J of Cellular Biochemistry

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In order to assess, in a controlled in vitro model, the differentiation potential of adult bone marrow derived stem cells we have developed a coculture procedure using adult rat cardiomyocytes and mesenchymal stem cells (MSCs) from transgenic GFP positive rats. We investigated in the cocultured MSCs the time course of cellular processes that are difficult to monitor in in vivo experiments. Adult rat cardiomyocytes and adult rat MSCs were cocultured for up to 7 days and analyzed by confocal microscopy. Several markers were studied by immunofluorescence technique. The fluorescent ST-BODIPY-Dihydropyridine was used to label calcium channels in living cells. Intracellular calcium was monitored with the fluorescent probe X-Rhod-1. Immunofluorescence experiments showed the presence of connexin-43 between cardiomyocytes and MSCs and between MSCs, while no sarcomeric structures were observed at any time of the coculture. We looked at the expression of calcium channels and development of voltage-dependent calcium signaling in cocultured MSCs. MSCs showed a time-dependent increase of labeling of ST-BODIPY-Dihydropyridine, reaching a relatively strong level after 72 h of coculture. The treatment with a non-fluorescent DHP, Nifedipine, completely abolished ST-BODIPY labeling. We investigated whether depolarization could modulate intracellular calcium. Depolarization-induced calcium transients increased in MSCs in relation to the coculture time. We conclude that MSCs cocultured with adult cardiomyocytes present preliminary evidence of voltage-dependent calcium modulation uncoupled with the development of nascent or adult myofibrils, thus showing a limited lineage specification and a low plasticity to differentiate in a full cardiomyocyte-like phenotype.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Limited plasticity of mesenchymal stem cells cocultured with adult cardiomyocytes

Gallo¹,

Ramella²,

Alloatti³

et al. 2006

J of Cellular Biochemistry

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“…: conception and design, financial support, provision of study material, data analysis and interpretation, and final approval of manuscript; H.C.C: conception and design, financial support, provision of study material, data analysis and interpretation, manuscript writing, and final approval of manuscript. cardiomyocytes [7][8][9], hepatocytes [10,11], and endothelial cells [12]. Especially, a large of body of evidence have indicated that mouse, rat, and human bone marrow MSCs can be induced to differentiate to neuron-like cells in culture [13][14][15][16] and further verified by the transplantation experiments in animal models of Parkinson's disease [17], stroke [18,19], cerebral ischemia [20], spinal cord injury [21], and Niemann-Pick disease [22].…”

Section: Introductionmentioning

confidence: 99%

Dedifferentiation-Reprogrammed Mesenchymal Stem Cells with Improved Therapeutic Potential

et al. 2011

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Stem cell transplantation has been shown to improve functional outcome in degenerative and ischemic disorders. However, low in vivo survival and differentiation potential of the transplanted cells limits their overall effectiveness and thus clinical usage. Here we show that, after in vitro induction of neuronal differentiation and dedifferentiation, on withdrawal of extrinsic factors, mesenchymal stem cells (MSCs) derived from bone marrow, which have already committed to neuronal lineage, revert to a primitive cell population (dedifferentiated MSCs) retaining stem cell characteristics but exhibiting a reprogrammed phenotype distinct from their original counterparts. Of therapeutic interest, the dedifferentiated MSCs exhibited enhanced cell survival and higher efficacy in neuronal differentiation compared to unmanipulated MSCs both in vitro and in vivo, with significantly improved cognition function in a neonatal hypoxic-ischemic brain damage rat model. Increased expression of bcl-2 family proteins and micro-RNA-34a appears to be the important mechanism giving rise to this previously undefined stem cell population that may provide a novel treatment strategy with improved therapeutic efficacy.

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“…We have previously reported in-vitro differentiation of human MSCs towards CLCs and shown that collagen V promoted adhesion and cardiac gene expression in CLCs (Shim et al, 2004;Tan et al, 2010). In the present study, we further examine the role of individual integrins in cardiac differentiation of CLCs.…”

Section: Introductionmentioning

confidence: 95%

Dynamic Relationships of Collagen Extracellular Matrices on Cardiac Differentiation of Human Mesenchymal Stem Cells

Yong¹,

Qian²,

Chung³

et al. 2012

New Advances in Stem Cell Transplantation

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Ex vivo differentiation of human adult bone marrow stem cells into cardiomyocyte-like cells

Cited by 175 publications

References 31 publications

Limited plasticity of mesenchymal stem cells cocultured with adult cardiomyocytes

Limited plasticity of mesenchymal stem cells cocultured with adult cardiomyocytes

Dedifferentiation-Reprogrammed Mesenchymal Stem Cells with Improved Therapeutic Potential

Dynamic Relationships of Collagen Extracellular Matrices on Cardiac Differentiation of Human Mesenchymal Stem Cells

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