Multilineage differentiation of human MSC after In utero transplantation

The Children's Institute for Surgical Science, The Children's Hospital of Philadelphia, PA 19104, USA.
Cytotherapy (Impact Factor: 3.29). 02/2001; 3(5):403-5. DOI: 10.1080/146532401753277571
Source: PubMed


Prenatal transplantation of stem cells is an exciting frontier for the treatment of many congenital diseases. The fetus may be an ideal recipient for stem cells, as it is immunologically immature and has rapidly proliferating cellular compartments that may support the engraftment of transplanted cells. Mesenchymal stem cells (MSC), given their ability to differentiate among multiple lineages, could potentially be used to treat diseases such as osteogenesis imperfecta, muscular dystrophy, and a variety of others that can be diagnosed in utero. We have shown, using a human-sheep in utero xenotransplantation model, that human MSC have the ability to engraft, differentiate into many tissue types, and survive for over 1 year in fetal lamb recipients. This observation warrants further studies of the behavior of MSC following systemic or site-directed transplantation.

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    • "Most studies on stem cell transplantation aimed at the treatment of myocardial infarction in animal models and human clinical trials have focused on the use of undifferentiated stem cells, so that cardiomyogenic differentiation would be expected to take place in vivo within a transplant recipient. Nonetheless, since undifferentiated MSCs tend to spontaneously differentiate into multiple lineages when transplanted in vivo [5,10], it is likely that such uncommitted stem cells may undergo unanticipated differentiation within infarcted myocardium. This can in turn reduce the clinical efficacy of the stem cell transplantation therapy for myocardial infarction. "
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    ABSTRACT: Human mesenchymal stem cells (hMSCs) are broadly discussed as a promising cell population amongst others for regenerative therapy of ischemic heart disease and its consequences. Although cardiac-specific differentiation of hMSCs was reported in several in vitro studies, these results were sometimes controversial and not reproducible. In our study we have analyzed different published protocols of cardiac differentiation of hMSCs and their modifications, including the use of differentiation cocktails, different biomaterial scaffolds, co-culture techniques, and two- and three-dimensional cultures. We also studied whether 5'-azacytidin and trichostatin A treatments in combination with the techniques mentioned above can increase the cardiomyogenic potential of hMSCs. We found that hMSCs failed to generate functionally active cardiomyocytes in vitro, although part of the cells demonstrated increased levels of cardiac-specific gene expression when treated with differentiation factors, chemical substances, or co-cultured with native cardiomyocytes. The failure of hMSCs to form cardiomyocytes makes doubtful the possibility of their use for mechanical reparation of the heart muscle.
    Full-text · Article · Nov 2009 · Journal of Negative Results in BioMedicine
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    • "A subset of stromal cells in bone marrow, which has been referred to as MS cells, is capable of producing multiple mesenchymal cell lineages, including bone, cartilage, fat, tendons, and other connective tissues [75] [90] [93] [94]. Recent reports show that human MSCs (HMSCs) also have the ability to differentiate into a diverse family of cell types that may be unrelated to their phenotypical embryonic origin, including muscle and hepatocytes [29] [63] [72] [92]. Although the potential therapeutic use of HMSCs in the CNS has been discussed [6] [95], and several in vivo transplantation studies showed neural and glial differentiation of HMSCs [53] [55], technologies to induce neural lineage from HMSC are not fully established. "
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    ABSTRACT: The use of stem cells for neuroreplacement therapy is no longer science fiction - it is science fact. We have succeeded in producing neural cells in the brain using both neural and mesenchymal stem cell transplantation and even systemic injection using a small molecular compound. We have seen the improvement of cognitive function in animal models following the application of these stem cell technologies. These results may promise a bright future for stem cell based neuroreplacement therapies for neurodegenerative diseases including Alzheimer's disease (AD). However, we have to consider the pathophysiological environments of individual diseases before clinical applications can be introduced. We must find the factors in the pathology that may affect stem cell biology and overcome the negative effects on neuroreplacement. Here, we discuss not only the potential for therapeutic applications of stem cell strategies in neuropathological conditions, but also how to overcome the adverse effects on the biology of stem cells due to the factors that are altered under AD pathology.
    Full-text · Article · Dec 2008 · Journal of Alzheimer's disease: JAD
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    • "A major limitation is that the majority of these studies have focused on the transplantation of undifferentiated stem cells, so that cardiomyogenic differentiation would be expected to take place in vivo within the transplant recipient. Because of the tendency of undifferentiated stem cells to spontaneously differentiate into multiple lineages when transplanted in vivo [10] [11], it is likely that only a small fraction of the transplanted stem cells would differentiate into the cardiomyogenic lineage. This could in turn reduce the clinical efficacy of stem cell transplantation therapy for myocardial regeneration. "
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    ABSTRACT: Most studies on stem cell transplantation therapy on myocardially infarcted animal models and phase-I human clinical trials have focused on the use of undifferentiated stem cells. There is a strong possibility that some degree of cardiomyogenic differentiation of stem cells in vitro prior to transplantation would result in higher engraftment efficiency, as well as enhanced myocardial regeneration and recovery of heart function. Additionally, this may also alleviate the probability of spontaneous differentiation of stem cells into undesired lineages and reduces the risk of teratoma formation, in the case of embryonic stem cells. The development of efficient protocols for directing the cardiomyogenic differentiation of stem cells in vitro will also provide a useful model for molecular studies and genetic manipulation. This review therefore critically examines the various techniques that could possibly be used to direct and control the cardiomyogenic differentiation of stem cells in vitro.
    Preview · Article · May 2004 · Cardiovascular Research
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