Engraftment of mesenchymal stem cells (MSCs) derived from adult bone marrow has been proposed as a potential therapeutic approach for postinfarction left ventricular dysfunction. However, limited cell viability after transplantation into the myocardium has restricted its regenerative capacity. In this study, we genetically modified MSCs with an antiapoptotic Bcl-2 gene and evaluated cell survival, engraftment, revascularization, and functional improvement in a rat left anterior descending ligation model via intracardiac injection. Rat MSCs were manipulated to overexpress the Bcl-2 gene. In vitro, the antiapoptotic and paracrine effects were assessed under hypoxic conditions. In vivo, the Bcl-2 gene-modified MSCs (Bcl-2-MSCs) were injected after myocardial infarction. The surviving cells were tracked after transplantation. Capillary density was quantified after 3 weeks. The left ventricular function was evaluated by pressure-volume loops. The Bcl-2 gene protected MSCs against apoptosis. In vitro, Bcl-2 overexpression reduced MSC apoptosis by 32% and enhanced vascular endothelial growth factor secretion by more than 60% under hypoxic conditions. Transplantation with Bcl-2-MSCs increased 2.2-fold, 1.9-fold, and 1.2-fold of the cellular survival at 4 days, 3 weeks, and 6 weeks, respectively, compared with the vector-MSC group. Capillary density in the infarct border zone was 15% higher in Bcl-2-MSC transplanted animals than in vector-MSC treated animals. Furthermore, Bcl-2-MSC transplanted animals had 17% smaller infarct size than vector-MSC treated animals and exhibited functional recovery remarkably. Our current findings support the premise that transplantation of antiapoptotic gene-modified MSCs may have values for mediating substantial functional recovery after acute myocardial infarction.

Neural stem cells (NSCs) are potential sources for cell therapy of neurodegenerative diseases and for drug screening. Despite their potential benefits, ethical and practical considerations limit the application of NSCs derived from human embryonic stem cells (ES) or adult brain tissue. Thus, alternative sources are required to satisfy the criteria of ready accessibility, rapid expansion in chemically defined media and reliable induction to a neuronal fate. We isolated somatic stem cells from the human periodontium that were collected during minimally invasive periodontal access flap surgery as part of guided tissue regeneration therapy. These cells could be propagated as neurospheres in serum-free medium, which underscores their cranial neural crest cell origin. Culture in the presence of epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2) under serum-free conditions resulted in large numbers of nestin-positive/Sox-2-positive NSCs. These periodontium-derived (pd) NSCs are highly proliferative and migrate in response to chemokines that have been described as inducing NSC migration. We used immunocytochemical techniques and RT-PCR analysis to assess neural differentiation after treatment of the expanded cells with a novel induction medium. Adherence to substrate, growth factor deprivation, and retinoic acid treatment led to the acquisition of neuronal morphology and stable expression of markers of neuronal differentiation by more than 90% of the cells. Thus, our novel method might provide nearly limitless numbers of neuronal precursors from a readily accessible autologous adult human source, which could be used as a platform for further experimental studies and has potential therapeutic implications.

While both cord blood and marrow CD133+ cells have some beneficial effects on post-injury angiogenesis and survival, only marrow cells appear to improve myocardial contractility.

Background: Siglec-7, a sialic acid binding inhibitory receptor expressed by NK cells is masked in vivo by a so far unknown ligand. It shows a strong binding prevalence for α-2,8-linked disialic acids in vitro.

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Neural stem cells are a potential source of cells for cell therapy of neurodegenerative diseases or drug screening. Ethical and practical considerations limit the application of neural stem cells derived from human embryonic stem cells or adult brain tissue. Therefore, alternative sources of adult human neural stem cells are of high interest for basic research as well as potential clinical use. These sources have to satisfy the demands of easy accession, rapid expansion in serum-free media and reliable induction to a neural fate. CD133 positive hematopoietic stem cells (HSCs) isolated from mobilized leukapheresis were cultured and expanded in the presence of epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF-2/bFGF) in serum-free medium. After two weeks of culture, neurosphere formation was observed. Subsequent culture in serum-free, EGF and FGF-2 containing medium resulted in large numbers of CD133−, Nestin+ and Sox-2+ neural stem cells. Neural stem cells derived from HSCs (hNSCs) are highly proliferative and are able to migrate in response to chemotactic stimuli described to induce migration of neural stem cells. We used immunocytochemical techniques and PCR to assess neural differentiation. Adherence to poly-D-lysine/laminin and growth factor deprivation resulted in cells of neuronal morphology and high expression of neuronal differentiation markers. We furthermore show that after retinoic acid treatment neuronal induction was greatly enhanced with more than 90% of cells expressing neuronal differentiation markers as beta-III-tubulin and neurofilaments. In addition, hNSCs were able to differentiate into cells of the glial lineage as shown by expression of glial fibrillary acidic protein (GFAP). Our novel method provides nearly limitless numbers of neural stem cells from an easily accessible autologous adult human source, which could be used as a starting point for further experimental studies and potential therapeutic use.