**1. Introduction**

Stromal cells make up some connective tissues for particular organs and give support by surrounding other tissues and organs. As result, stromal cells provide support, structure, and anchoring for many organs inside the body. The generic term "stromal cells" clearly the phenotypic and functional complexity of these cells. In addition, to their main functions in helping support organs and acting as connective tissues, stromal cells respond with metabolic adaptations to different inductions factors and play an important role in the microenvironment [1]. Stromal cells are able to react to physical and chemical signals of tissue damage. Physical stress such as mechanical stress activates channels (SACs) on the cell membrane [2].

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

On cells attached to an extracellular matrix, SACs initiate the remodeling of cell membrane structures called integrins. Membrane receptors rapidly send signals to the nucleus which initiate the synthesis of proteins, which in turn interact with cell metabolism and the surrounding environment to induce the modulation of recovery of parenchymal tissue function. Fibroblasts, pericytes, and stem cells are among the most common types of stromal cells. In this chapter, we analyze the membrane markers of stem cells and assess their capacity to influence surrounding tissues and recover tissue functionality.

AP1 transcription factors are also associated with tissue regeneration. Cyclin D is a protein involved in regulating cell cycle progression by regulating the G1–to-S phases [9]. AP1 also induces CREB, another transcription factor responsible for increasing or decreasing the transcription of downstream genes [10]. The presence of CD73 in the cell membrane allows this enzyme to release ADO from extracellular AMP. ADO then binds to a membrane receptor associated with the G protein. Activation of the G protein induces a phosphorylation cascade that allows the activation of transcription factors. The target genes of these transcription factors are those involved with the cell cycle, the synthesis of extracellular matrix, and vascular growth factors (**Figure 1**). Nevertheless, activation of these receptors induces variable

Adult Stem Cell Membrane Markers: Their Importance and Critical Role in Their Proliferation…

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The pathway generates the liberation of extracellular ADO and could be responsible for the angiogenic effects observed in stem cell transplantation. Because of the dephosphorylate enzymatic activity of CD73 on AMP, the pathway induces the synthesis of VEGF. Indirectly, CD73 is responsible for the angiogenic capacity of stem cells as generating ADO by autocrine signaling will consequently stimulate the production of VEGF, a pro-angiogenic factor. For example, in skeletal muscle cells, activated PKA phosphorylates enzymes involved in glycogen metabolism which simultaneously trigger the breakdown of glycogen to glucose and inhibit glycogen synthesis, thereby increasing the amount of glucose available to muscle cells within seconds. In macrophages, it also induces the synthesis of angiogenic factors, such as VEGF and the proliferation of human retinal endothelial cells [11–13]. The pathway also plays an important role in the proliferation of endothelial cells. Stimulation of A2A receptors could be responsible for wound healing by stimulating both angiogenesis and matrix production [14]. Montesinos et al. [15] proposed that ADOA2A receptor stimulation by ADO promotes the recruitment of circulating bone marrow-derived endothelial precursor cells and differentiation into endothelial cells. CD73 serves as a costimulatory molecule in activating

**Figure 1.** Schematic CD73 signaling pathways. The activity of ectonuclease on extra-cytoplasmic AMP releases (ADO). ADO binds to its receptor which in turn generates the activation of the G protein and triggers the phosphorylation cascade up to transcription factors that will induce the expression of genes responsible for the synthesis of collagen and

responses in different cells.

T cells [16].

vascular endothelial growth factors (VEGF).
