The Role of Adipose-Derived Stem Cells in Hydrogels in Facilitating and Promoting Angiogenesis in Response to Ischemia
Introduction. Ischemia is the blockage of arterial supply to live tissue, and prolonged ischemia leads to various types of tissue necrosis1,2, which occurs in response to the release of cytokines. Angiogenesis is a response to ischemia, which is the growth of new vasculature. This process helps replenish the much-needed oxygen supply to the oxygen-deprived tissue. Adipose-derived stem cells (ADSCs) are one of the most easily extractable stem cells in the human body, and has been shown to promote the expression of pro-angiogenic factors3. Additionally, hydrogels are currently being explored as possible vehicles for administration for stem cells, differentiated cells, or even pro-angiogenic factors to induce tissue repair, mainly because they have a potential to mimic the extracellular matrix and provide the anchorage and matrix-cell adhesion that a cell needs in order to survive and divide. Methods. ADSCs were isolated from human adipose tissue, and were plated on different surfaces and incubated, after which PCR analysis showed the levels of expression of pro-angiogenic factors IL-8, VEGF, bFGF, and SDF-13. Another experiment took a methacrylated gelatin (GelMA), which was made into a rigid crosslinked structure, and a VEGF-mimicking peptide (AcQK) was covalently linked into the system, after which HUVEC cells were embedded in the gel, and tested for expression of vascular-specific genes, like CD-344. A third experiment was investigating the influence on the expression of a pro-angiogenic factor, glial-derived neurotrophic factor (GDNF)5. Finally, a fourth experiment used a hydrogel with embedded ADSCs, and compared it to controls, assessing for its blood vessel growth and vessel branching6. Results. ADSCs showed a significantly increased expression of mRNA encoding the pro-angiogenic factor IL-8, especially when embedded in a hydrogel. It was also shown that GDNF was important for neovascularization, as GDNF was able to induce neovascularization with HUVEC cells in either ADSC-conditioned media or alone5. Thirdly, VEGF-mimicking peptide induced the expression of CD-34, which led to increased neovascularization4. Lastly, using the chick aortic ring and chorioallontoic membrane assay, it was found that hydrogels loaded with VEGF or ADSCs had more blood vessel growth and branching when compared to unloaded hydrogels6. Conclusions. It is safe to say that proper neovascularization requires an accurate microenvironment. Also, many pro-angiogenic factors such as GDNF and IL-8 have been concluded to play a critical role in angiogenesis, and the synergies amongst hydrogels, ADSCs, and VEGF-like peptides must be kept in consideration when preparing biotechnology that promotes optimal neovascularization.
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