**1. Introduction**

Our immune system has developed to fight against invaders. Pathogenic invaders are microorganisms including virus, bacteria, fungus and amoeba.

In species development, innate immune system appeared first, then after jowed fish acquired immune system developed. Once microorganisms infects in organs, cells belonging to innate immune system such as neutrophils and macrophages move to the site of infection. Microor‐ ganisms are sensed by pattern‐recognition receptors (PRRs) of the innate immune system including dendritic cells (DC).These cells phagocytize infectious agents and produce cytokines and chemokines, which induce tissue inflammation. In phagolysozome of DC, the proteins, which constitute the microorganisms, are degraded. These DC migrates to lymph node and present the microorganisms antigens to T cells, which are central of adaptive immune responses.

Similar to the eradication of pathogens, the inflammatory response is also crucial for tissue and wound repair and called sterile inflammation. Host‐derived non‐microbial stimuli are released following tissue injury or cell death. These endogenous molecules have been termed damage‐associated molecular patterns (DAMPs). DAMPs are normally present intracellular and are therefore hidden from recognition by the immune system. Once tissues are injured these molecules are released into the extracellular environment by dying cells and trigger inflammation under sterile conditions [1] (Figure 1).

© 2013 Isobe et al.; licensee InTech. This is an open access article 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. © 2013 Isobe et al.; licensee InTech. This is a paper 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.

> adhesion and recruitment. Within 30 min. neutrophils migrate to the site of wound, which phagocytize dead cells and cellular debris and clear tissue. Then neutrophils are themselves phagocytized by tissue macrophages. Although M1 macrophages damage tissue cells pro‐ ducing tissue‐damaging proteases, which are primarily kill microorganisms, M1 macrophages also engulf damaged tissue cells. Then M2 macrophages migrate from blood vessel to repair tissue. Neutrophils have specific cell surface antigens called, Gr‐1. In murine model of wound repair (Figure 2), we depleted neutrophils by anti‐GR‐1 antibody. Although in young mice the kinetics of wound healing was not different by the depletion of neutrophils, the depletion of neutrophils by anti‐Gr‐1 antibody dramatically delayed wound healing in aged mice [4]. Bone marrow has both matured neutrophils and macrophages. First, we found that in splenectom‐ ized mice, bone marrow, spleen and thymus injection accerated wound healing (Figure 3). We transplanted bone marrow cells from GFP mice (C57BL/6 background) to C57BL/6 mice. We found that bone marrow cells injection accelerated wound healing and GFP positive neutro‐ phils and macrophages migrated to the wound tissue. Because wound healing of aged mice is relatively inefficient, we transplanted young bone marrow cells to aged mice. We found that young bone marrow cells enhanced wound healing of aged mice [5, 6]. In case of microorgan‐ isms acquired immunity help to phagocytize invader. By microorganism's infections, immu‐ noglobulin specific for the microorganisms bind to the surface and induce phagocytosis mediated by Fc receptors.We examined whether B cells, which produce antibodies to damaged tissues, might be engaged in the process of wound healing. We found that wound healing in splenectomized nude mice was delayed and the transfer of B cells accelerated wound healing in splenectomized mice. Further we detected several autoantibodies binding to wounded tissues [7] (Fig.4). Advancing age gradually decreased the strength of IgG1 autoantibodies, which bind to wounded tissues, although the strength of IgM autoantibodies was relatively

Tissue Damage and Repair Caused by Immune System and Personalized Therapy of Failed Organs by Stem Cells 209

As a mucosal wound repair model we used dextran sulfate sodium (DSS). Colitis may result from DSS toxicity to colonic epithelial cells. DSS is commonly used in rodent models to chemically induce acute intestinal inflammation, and the DSS‐induced colitis is characterized by weight loss, bloody diarrhea, epithelial cell damage, and immune cell infiltration, as well as an increased production of inflammatory mediators including TNF‐α, IL‐6, IL‐12, and interferons. Colitis was induced by oral administration of DSS to two months old C57BL/6 mice at 2 % (w/v)in drinking water ad libitum forfive days followed by normal drinking water. By this schedule, mice almost completely recovered. Interestingly at recovery phase of DSS‐ induced colitis, we observed strong up‐regulation of innate immune cells having Gr1+

cell surface maker in spleen and bone marrow. Transplantation of splenic DSS‐derived

CD11b+ cells into DSS‐treated mice improved colitis and promoted efficient colonic mucosal healing [8] (Figure 5). Anti‐Gr‐1 antibody treatment worsened the DSS‐ administered colitis. These results indicate that Gr1+CD11b+ cells induced by DSS worked to repair colon

CD11b

stable by advancing age [5, 6].

wound healing and repair colitis [9].

**2.2. DSS‐induced colitis**

+

Gr1+

**Figure 1.** Damaged cells by various stimuli produce DAMPs, which activate tissue resident macrophages and dendritic cells. Activated innate cells produce pro-inflammatory cytokines.
