Kevin Varghese

 Introduction. Ischemia is the blockage of arterial supply to live tissue, and prolonged ischemia leads to various types of tissue necrosis^1,2, 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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5. Zhong Z, Gu H, Peng J, et al. GDNF secreted from adipose-derived stem cells stimulates VEGF-independent angiogenesis. Oncotarget. 2016;7(24):36829-36841.
6. Eke G, Mangir N, Hasirci N, MacNeil S, Hasirci V. Development of a UV crosslinked biodegradable hydrogel containing adipose derived stem cells to promote vascularization for skin wounds and tissue engineering. Biomaterials. 2017;129:188-198. doi:https://doi.org/10.1016/j.biomaterials.2017.03.021