[Frontiers in Bioscience 14, 1433-1470, January 1, 2009]
Adult stem cells and repair through granulation tissue

Lucio Diaz-Flores Jr. 1, Ricardo Gutierrez1, Juan Francisco Madrid2, Hilda Varela1, Francisco Valladares1, Lucio Diaz-Flores1

2Department of Pathology, Histology and Radiology, School of Medicine, La Laguna University, Canary Islands, Spain, 2Department of Cell Biology and Histology, School of Medicine, University of Murcia, Spain

TABLE OF CONTENTS

1. Abstract
2. Introduction
2.1.ASC and TAC
2.2.Repair through granulation tissue (RTGT)
2.3.ASC and TAC in RTGT
3.Regions with repair through granulation tissue capacity
4.Events in RTGT
5.Inflammatory phenomena associated with RTGT, with particular reference to recruitment of cells, and release and mobilization of growth factors
6.Stem cells and RTGT
6.1.Macrophages and progenitor cells
6.2.Endothelium and pericytes (preexisting microvasculature and new capillaries), ASC and TAC
6.2.1.Endothelium, ASC and TAC
6.2.1.1.Preexisting endothelium as progenitor cells
6.2.1.2.Other endothelial cell precursors (Endothelium as descendent cells)
6.2.2.Pericytes, ASC and TAC
6.2.2.1.Preexisting pericytes as precursor cells
6.2.2.2.Other pericyte precursors (pericytes as descendent cells)
6.3.Fibroblast/myofibroblasts, ASC and TAC
6.3.1.Preexisting fibroblasts as precursor cells
6.3.2.Other fibroblasts/myofibroblasts precursors (fibroblasts/myofibroblasts as descendent cells)
7.Involutive phenomena: RTGT as a "paracrine transitional organ"
8.RTGT and Cellular differentiation, dedifferentiation, transdifferentiation and fusion
9.ASC, RTGT and tissue engineering
10. ASC and RTGT in Pathology
10.1. ASC, Organization, abnormal RTGT and fibrosis
10.2. ASC, RTGT and atherosclerosis
10.3. ASC, RTGT and tumor stroma
11. Overview and clinical promise 12.References

1. ABSTRACT

Macrophage recruitment and proliferation of both small vessels (endothelium and pericytes) and fibroblast-myofibroblasts are the fundamental and provisional cellular findings in repair through granulation tissue (RTGT).Endothelium and pericytes of preexisting microvasculature may act as progenitor cells of new endothelial cells and new pericyte-fibroblast-myofibroblasts, respectively.Likewise, fibroblasts may be progenitors of themselves, and of myofibroblasts and pericytes. Moreover, all these cells may originate from circulating progenitor cells or other progenitor cells..According to this extensive cellular plasticity, this work reviews the adult stem cells (ASC) and transit- amplifying cells (TAC) related to the principal cellular components of RTGT.Moreover, we hypothesize that the perivascular region, with a heterogeneous pericyte-like cellular population, including pericytes, perivascular fibroblasts and homing cells from the bone marrow (fibrocytes and bone marrow mesenchymal cells), is the niche of progenitor cells in RTGT and the substrate of regulatory mechanisms (perivascular niche hypothesis).We also highlight RTGT as a "paracrine transitional organ" during involutive phenomena and cellular differentiation.Furthermore, we consider the combined role of both systems (ASC-TAC and RTGT) in tissue engineering and in pathological processes, such as fibrosis, organization, atherosclerosis, and tumor stroma.