Adipose-Derived Stem Cells: Angiogenetic Potential and Utility in Tissue Engineering.

Adipose tissue (AT) is a large and important energy storage organ as well as an endocrine organ with a critical role in many processes. Additionally, AT is an enormous and easily accessible source of multipotent cell types used in our day for all types of tissue regeneration. The ability of adipose-derived stem cells (ADSCs) to differentiate into other types of cells, such as endothelial cells (ECs), vascular smooth muscle cells, or cardiomyocytes, is used in tissue engineering in order to promote/stimulate the process of angiogenesis. Being a key for future successful clinical applications, functional vascular networks in engineered tissue are targeted by numerous in vivo and ex vivo studies. The article reviews the angiogenic potential of ADSCs and explores their capacity in the field of tissue engineering (TE).

Effects of Placenta-Derived Human Amniotic Epithelial Cells on the Wound Healing Process and TGF-ß Induced Scar Formation in Murine Ischemic-Reperfusion Injury Model.

BACKGROUND: Pressure ulcers (PUs), a result of ischemic reperfusion (IR) injuries, are prevalent skin problems which show refractoriness against standard therapeutic approaches. Besides, scar formation is a critical complication of ulcers that affects functionality and the skin's cosmetic aspect. The current study aimed to investigate the effects of placenta-derived human amniotic epithelial cells (hAECs), as important agents of regenerative medicine and stem cell therapy, on accelerating the healing of IR ulcers in mice. We also evaluated the effects of these cells on reducing the TGFß-induced scar formation. METHODS: Male Balb/c mice at the age of 6-8 weeks were subjected to three IR cycles. Afterward, the mice were divided into three experimental groups (n = 6 per group), including the control group, vehicle group, and hAECs treatment group. Mice of the treatment group received 100 µL of fresh hAECs 1 × 106 cell/ml suspension in PBS. Afterward, mice were assessed by histological, stereological, molecular, and western blotting techniques at 3, 7, 14, and 21 days after wounding. RESULTS: The histological and stereological results showed the most diminutive scar formation and better healing in the hAECs treated group compared to control group. Furthermore, our results demonstrated that the expression level of Col1A1 on days 3, 14, and 21 in the hAECs treated group was significantly lower than control. Additionally, injection of hAECs significantly reduced the expression level of Col3A1 on days 3, 7, and 21 while increased Col3A1 on the day 14. Otherwise, in the hAECs treated group, the expression levels of VEGFA on days 7 and 14 were higher, which showed that hAECs could promote angiogenesis and wound healing. Also, cell therapy significantly lowered the protein levels of TGF-ß1 on day 14, while the protein level of TGF-ß3 on day 14 was significantly higher. This data could demonstrate the role of hAECs in scar reduction in IR wounds. CONCLUSION: These results suggest that hAECs can promote re-epithelialization and wound closure in an animal model of PU. They also reduced scar formation during wound healing by reducing the expression of TGF-ß1/ TGF-ß3 ratio.

The differentiation effect of bone morphogenetic protein (BMP) on human amniotic epithelial stem cells to express ectodermal lineage markers.

Stem cells are a promising tool for treatment of a variety of degenerative diseases. Human amniotic epithelial stem cells (hAECs) have desirable and unique characteristics that make them a proper candidate for cell therapy. In this study, we have investigated the effects of BMP-4 (bone morphogenetic protein-4) and its inhibition on differentiation of AECs into ectodermal lineages. Analysis of AEC-derived ectodermal lineages (neurons and keratinocytes) was performed by using flow cytometry technique for Map2 and ß-tubulin (as neuron markers), Olig2 and MBP (as oligodendrocyte markers), and K14 and K10 (as keratinocyte markers). The results of this study illustrated that noggin (as BMP antagonist), BMP4, and both BMP4 and heparin (together or separately) increased neural and keratinocyte marker expression, respectively. The expression of markers MAP2, olig2, and K14 in hAECs has been significantly decreased 21 days after exposure to differentiation medium (without growth factors) compared with isolation day, which supports the hypothesis that AECs can be dedifferentiated into pluripotent cells. Moreover, activation and inhibition of BMP signaling have no effects on viability of hAECs. The results of this study showed that BMP signaling and its inhibition are the key factors for ectodermal lineage differentiation of amnion-derived stem cells.

Amniotic membrane and its epithelial and mesenchymal stem cells as an appropriate source for skin tissue engineering and regenerative medicine.

One of the main goals of tissue engineering and regenerative medicine is to develop skin substitutes for treating deep dermal and full thickness wounds. In this regard, both scaffold and cell source have a fundamental role to achieve exactly the same histological and physiological analog of skin. Amnion epithelial and mesenchymal cells possess the characteristics of pluripotent stem cells which have the capability to differentiate into all three germ layers and can be obtained without any ethical concern. Amniotic cells also produce different growth factors, angio-modulatory cytokines, anti-bacterial peptides and a wide range of anti-inflammatory agents which eventually cause acceleration in wound healing. In addition, amniotic membrane matrix exhibits characteristics of an ideal scaffold and skin substitute through various types of extracellular proteins such as collagens, laminins and fibronectins which serve as an anchor for cell attachment and proliferation, a bed for cell delivery and a reservoir of drugs and growth factors involved in wound healing process. Recently, isolation of amniotic cells exosomes, surface modification and cross-linking approaches, construction of amnion based nanocomposites and impregnation of amnion with nanoparticles, construction of amnion hydrogel and micronizing process promoted its properties for tissue engineering. In this manuscript, the recent progress was reviewed which approve that amnion-derived cells and matrix have potential to be involved in skin substitutes; an enriched cell containing scaffold which has a great capability to be translated into the clinic.