Differentiation Ability Of Mesenchymal Stem Cells Research Articles

In Vitro and In Vivo Comparison of Different Types of Rabbit Mesenchymal Stem Cells for Cartilage Repair.

Systematic studies indicate a growing number of clinical studies that use mesenchymal stem cells (MSCs) for the treatment of cartilage lesions. The current experimental and preclinical study aims to comparatively evaluate the potential of MSCs from a variety of tissues for the treatment of cartilage defect in rabbit's knee which has not previously been reported. In this experimental study, MSCs isolated from bone marrow (BMMSCs), adipose (AMSCs), and ears (EMSCs) of rabbits and expanded under in vitro culture. The growth rate and differentiation ability of MSCs into chondrocyte and the formation of cartilage pellet were investigated by drawing the growth curve and real-time polymerase chain reaction (RT-PCR), respectively. Then, the critical cartilage defect was created on the articular cartilage (AC) of the rabbit distal femur, and MSCs in collagen carrier were transplanted. The studied groups were as the control (only defect), sham (defect with scaffold), BMMSCs in the scaffold, EMSCs in the scaffold, and EMSCs in the scaffold with cartilage pellets. Histological and the gene expression analysis were performed following the transplantation. Based on our comparative in vitro investigation, AMSCs possessed the highest growth rate, as well as the lowest chondrogenic differentiation potential. In this context, MSCs of the ear showed a significantly higher growth rate and cartilage differentiation potential than those of bone marrow tissue (P<0.05). According to our in vivo assessments, BMMSC- and EMSC-seeded scaffolds efficiently improved the cartilage defect 4 weeks post-transplantation, while no improvement was observed in the group contained the cartilage pellets. It seems that the ear contains MSCs that promote cartilage regeneration as much as the conventional MSCs from the bone marrow. Considering a high proliferation rate and easy harvesting of MSCs of the ear, this finding could be of value for the regenerative medicine.

In Vitro and In Vivo Comparison of Different Types of Rabbit Mesenchymal Stem Cells for Cartilage Repair

Objective Systematic studies indicate a growing number of clinical studies that use mesenchymal stem cells (MSCs) for the treatment of cartilage lesions. The current experimental and preclinical study aims to comparatively evaluate the potential of MSCs from a variety of tissues for the treatment of cartilage defect in rabbit’s knee which has not previously been reported. Materials and Methods In this experimental study, MSCs isolated from bone marrow (BMMSCs), adipose (AMSCs), and ears (EMSCs) of rabbits and expanded under in vitro culture. The growth rate and differentiation ability of MSCs into chondrocyte and the formation of cartilage pellet were investigated by drawing the growth curve and real-time polymerase chain reaction (RT-PCR), respectively. Then, the critical cartilage defect was created on the articular cartilage (AC) of the rabbit distal femur, and MSCs in collagen carrier were transplanted. The studied groups were as the control (only defect), sham (defect with scaffold), BMMSCs in the scaffold, EMSCs in the scaffold, and EMSCs in the scaffold with cartilage pellets. Histological and the gene expression analysis were performed following the transplantation. Results Based on our comparative in vitro investigation, AMSCs possessed the highest growth rate, as well as the lowest chondrogenic differentiation potential. In this context, MSCs of the ear showed a significantly higher growth rate and cartilage differentiation potential than those of bone marrow tissue (P<0.05). According to our in vivo assessments, BMMSC- and EMSC-seeded scaffolds efficiently improved the cartilage defect 4 weeks post-transplantation, while no improvement was observed in the group contained the cartilage pellets. ConclusionIt seems that the ear contains MSCs that promote cartilage regeneration as much as the conventional MSCs from the bone marrow. Considering a high proliferation rate and easy harvesting of MSCs of the ear, this finding could be of value for the regenerative medicine.

Differentiation Potential of Mesenchymal Stem Cells Is Related to Their Intrinsic Mechanical Properties.

PurposeThe differentiation properties of stem cells are not yet fully understood due to their close association with multiple environmental and extrinsic factors. This study investigates the differentiation properties of mesenchymal stem cells (MSCs) and correlates them with their intrinsic mechanical properties.MethodsA total of 3 different types of MSCs, namely bone marrow-derived MSCs (BMSCs), umbilical cord-derived MSCs (UCSCs), and adipose-derived MSCs (ADSCs) were evaluated. These 3 MSCs were individually differentiated into adipocytes and osteoblasts for 3 weeks. The mechanical properties of the MSCs and differentiated cells were determined by atomic force microscopy.ResultsADSCs showed the greatest ability to differentiate into adipocytes, followed by BMSCs and UCSCs. While UCSCs differentiated readily into osteoblasts, BMSCs and ADSCs were less likely to undergo this differentiation. UCSCs were the “hardest” cells, while ADSCs were the “softest.” The cells differentiated from “hard” MSCs were stiffer than the cells differentiated from “soft” MSCs, irrespective of lineage specification.ConclusionsThe differentiation ability of MSCs and the mechanical properties of the differentiated cells were closely linked. However, there were no significant correlations regarding changes in the mechanical properties between the nuclear region and the cytoplasm during differentiation.

Secretome of Human Fetal Mesenchymal Stem Cell Ameliorates Replicative Senescen.

Autologous mesenchymal stem cells (MSC) are widely used cell source for cell-based tissue repair and regeneration, but replicative senescence and the associated loss of cellular activity during in vitro expansion limit their therapeutic potential. How to preserve or even enhance the proliferation and differentiation ability of MSC from aged donors without genetic modification remains a challenge to meet clinical need. MSC isolated from human fetal tissues (hFMSC) exhibit higher proliferation and differentiation activities even in prolonged in vitro culture, which might be modulated by autocrine/paracrine action. In the present study, we hypothesized that the bioactive factors secreted by hFMSC, collectively named as hFMSC secretome (HFS), could possess beneficial effect on human adult MSC (hAMSC) undergoing replicative senescence, thus promoting their capability of proliferation and differentiation. HFS was prepared by centrifugation of hFMSC conditioned medium, followed by column-based concentration, and the total protein content of the HFS was quantified to standardize treatment concentration. When compared with hAMSC secretome (HAS), HFS treatment significantly reduced senescence associated-β-galactosidase expression and activity (senescence marker) and enhanced cell proliferation and osteogenic differentiation potential of hAMSC in prolonged in vitro culture. Cellular studies revealed concomitant activation of sirt1 and foxo3a in hAMSC after HFS treatment, which was associated with upregulation of p21 and downregulation of bax and p53. The changes of these senescence associated markers suggested that HFS, but not HAS, could ameliorate replicative senescence of hAMSC in vitro. In nude mice, HFS pretreatment restored the osteogenic ability of senescent hAMSC. Tumor xenograft model revealed that HFS did not promote tumor growth. In conclusion, this study suggests that HFS could be an effective and safe method to overcome replicative senescence and facilitate the therapeutic potential of hAMSC.

Hypoxia promotes proliferation and osteogenic differentiation potentials of human mesenchymal stem cells

Mesenchymal stem cells (MSCs), which can be isolated from bone marrow and other somatic tissues, are residing in an environment with relative low oxygen tension. The purpose of this study is to investigate the effects of hypoxia on MSCs, and we hypothesize that oxygen concentration regulates the intricate balance between cellular proliferation and commitment towards differentiation. In this study, human bone marrow-derived MSCs were cultured under hypoxia with 1% O(2). The proliferation ability of MSCs was increased after a 7-day hypoxic culture period. Migration assay showed that hypoxia enhanced the migration capabilities of MSCs. Moreover, expression of stemness genes Oct4, Nanog, Sall4 and Klf4 was increased under hypoxia. Furthermore, the differentiation ability of MSCs under hypoxia favored osteogenesis while adipogenesis was inhibited during a 4-week induction period. Cytokine antibody array analysis showed that a number of growth factors were up-regulated after a 7-day hypoxic incubation and the differential expression of growth factors may account for the increased proliferation and osteogenic potentials of MSCs under hypoxic condition. Taken together, hypoxia provides a favorable culture condition to promote proliferation as well as osteogenesis of MSCs through differential growth factor production.