However, it has also been reported that MSC transplantations may result in some dangerous disadvantages, such as the formation of teratomas by MSCs. dermal fibroblasts and keratinocytes to promote re-epithelialization and angiogenesis and, as a result, facilitates wound healing of rat pores and skin wounds [5]. Table 3 Paracrine factors of transplanting BMSCs for cells restoration
TGF-, FGF-2, angiopoietin-2, VEGF-1Rat myocardial infarction modelTriggered Tautomycetin angiogenic and migratory effects at the site of the infarct FLJ31945 Tautomycetin to promote myocardial healing and improve the cardiac function.[1]NGF, HGF, IL-10, IL1-RA NOD/SCID mouse modelContributed to the prevention of apoptosis, increasing cell proliferation in the damaged liver.[86]TGF-1, VEGFMouse burn injury modelAssisted in burn wound healing.[2]IGF-1Mouse acute kidney injury modelExerted beneficial effects on tubular cell restoration in acute kidney injury.[87]Angiogenin, IL-8, MCP-1, and VEGFMouse hind limb ischemia modelRepresented efficient biomarkers for predicting vascular regenerative effectiveness of MSCs.[4]IGF-1, VEGF, EGF, and bFGFRat middle cerebral artery occlusion ischemia modelInduced functional improvement, reduced infarct volume, and showed neuroprotection in ischemic rats.[88]TGF- Rat stroke modelSuppressed immune propagation in the ischemic rat brain.[89]SDF-1, VEGF, HGF, and IL-6Rat pores and skin wound modelEnhanced the activity of dermal fibroblasts and keratinocytes to promote re-epithelialization and angiogenesis and, consequently, promoted wound healing.[5] Open in a separate window 4.1.2. Conditioned Medium from BMSCs for Cells Repair MSCs have become a good cell source and are widely employed in the development of a variety of regenerative medicine and tissue restoration strategies. However, it has also been reported that MSC transplantations may result in some dangerous disadvantages, such as the formation of Tautomycetin teratomas by MSCs. To avoid this possible safety concern, recent attention has been focused on using BMSC conditioned medium (BMSC-CM), containing internal cytokines/mediators secreted by BMSCs, to develop a cell-free restorative approach in stem cell therapy (Table 4). Kawai et al. clarified that the use of BMSC-CM is an alternate therapy for periodontal cells regeneration, because several cytokines (IGF-1, VEGF, TGF-1, and HGF) were included in BMSC-CM that contribute to wound healing and angiogenesis [3]. The intramuscular injection of conditioned medium (including IL-6 and IL-8) derived from TNF–treated human being BMSCs into a rat hindlimb ischemia model stimulated angiogenesis and cells restoration [88]. It was found that conditioned press from human being umbilical wire blood-derived mesenchymal stem cells (UC-MSC-CM) consist of many pores and skin rejuvenation-associated paracrine factorssuch as epithelial growth element (EGF), bFGF, PDGF, HGF, collagen type 1, and, especially, one of the rejuvenation factors, namely, growth differentiation element-11 (GDF-11)which can induce pores and skin wound healing by increasing the growth and ECM production of human being dermal fibroblasts [89]. Fibroblasts are the main cells involved in wound restoration. Under dermal UC-MSC-CM activation, the characteristics of adult fibroblasts modified to produce high ratios of collagen types III and I and a high MMPs/TIMPs ratio, suggesting that UC-MSC-CM may be a feasible strategy to promote cutaneous restoration and a potential way to heal damaged sites [90]. Table 4 Conditioned medium from BMSCs for cells restoration
IGF-1, VEGF, TGF-1 and HGFRat periodontal defect modelContributed to many processes of complicated periodontal tissue regeneration.[3]IL-6, IL-8Rat hind limb ischemia modelStimulated angiogenesis and cells restoration through an increase in homing of human being wire blood-derived endothelial progenitor.[90]EGF, bFGF, PDGF, HGF, collagen type 1, and GDF-11In vivo human being testStimulated pores and skin rejuvenation by increasing growth and ECM production.[91]Collagen types III and I and a high MMPs/TIMPs ratioMouse pores and skin excisional wound modelAccelerated healing, with fewer scars compared with control organizations.[92] Open in a separate windowpane 4.2. Directed Differentiation of BMSCs and Cells Restoration Apart from the paracrine mechanism, another key mechanism of MSCs in cells restoration is their directed differentiation.