Specific Roles and Properties of Mesenchymal Stem Cells

[73] Lee H, Kim M, Park YH, et al. Dexamethasone downregulates SIRT1 and IL6 and upregulates EDN1 genes in stem cells derived from gingivae via the AGE/RAGE pathway. Biotechnology Letters. 2018;40(3):509-519. DOI: 10.1007/s10529-017-2493-0

Update on Mesenchymal and Induced Pluripotent Stem Cells

[74] Jiang CM, Liu J, Zhao JY, et al.

immunomodulatory properties of human gingiva-derived mesenchymal stem cells. Journal of Dental Research. 2015;94(1):69-77. DOI: 10.1177/

Effects of hypoxia on the

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**Chapter 6**

**Abstract**

**1. Introduction**

*and Reza Rahbarghazi*

The Angiogenic Paracrine Potential

of Mesenchymal Stem Cells

stem cells to modulate angiogenesis in the target tissues.

*Jafar Rezaie, Morteza Heidarzadeh, Mehdi Hassanpour,* 

Tissue engineering and regenerative medicine are branches of biomedical sciences that facilitate the use of cells and biocompatible scaffolds in favor of tissue restoration. In this regard, restoration and maintenance of angiogenesis and blood supplementation could be an effective strategy for injured tissue removal, accelerating healing rate, and successful transplantation of cells and scaffolds into target sites. It has been elucidated that mesenchymal stem cells have the potency to promote angiogenesis via paracrine activity and trans-differentiation into the endothelial lineage. In this chapter, we highlighted the paracrine property of mesenchymal

**Keywords:** mesenchymal stem cells, angiogenesis, paracrine activity, exosomes

Angiogenesis, termed as neovascularization, is defined as de novo vascularization from the pre-existing vascular network and activated in response to numerous pathological and physiological stimuli, playing critical roles during development and tissue repair [1]. Recent advances in the field of stem cell research, notably MSCs, have opened new horizons to human medicine in the promotion of angiogenesis and restoration and salvage of ischemic tissues [2]. MSCs actively participate in angiogenesis via direct differentiation, cell contact interaction with endothelial lineage, and releasing pro-angiogenic factors via a paracrine manner [3]. Due to the low survival and differentiation rate of MSCs posttransplantation into ischemic microenvironment, it is proposed that the paracrine activity is the principal mechanism for the therapeutic outcome [4]. It has been well-established that stem cell-secreted growth factors are responsible for, at least in part, therapeutic effects. As a matter of fact, MSC-derived secretome is thought to be a suitable alternative therapeutic modality to MSCs posttransplantation. At present, the underlying mechanisms by which MSC secretomes contribute to tissue healing and angiogenesis are not fully addressed and many efforts are needed to fill knowledge gaps by experimental animal research and clinical trials prior to application to human medicine [5, 6]. Paracrine factors could increase the blood supplement of damaged tissues via the activation and recruitment of resident/circulating stem cells and progenitor cells [7, 8]. Several experiments detected the pro-angiogenic

*Hassan Amini, Elhameh Shokrollahi, Mahdi Ahmadi* 
