. Author manuscript; available in PMC: 2015 Jul 3.

Published in final edited form as: Cell Stem Cell. 2014 Jul 3;15(1):14–25. doi: 10.1016/j.stem.2014.06.009

Table 1. Summary of the regenerative capacity, mechanisms, and disease states of representative mammalian tissues.

The process of regeneration is summarized for six different tissues, each with varying regenerative capacities: skin, heart, skeletal muscle, CNS, liver and bone. For each, steps that have the potential to be influenced by immunity are listed as well as the disease state and summary of immune targeted therapeutics.

TISSUE	DEBRIS CLEARNACE MECHANISM	PROGENITOR CELL POOL	IMMUNE-DERIVED STIMULI	POLARIZATION & HETEROGENITY	DISEASE STATE DUE TO FAILED REGENERATION	DEFECT	DRUGS TARGETING IMMUNITY
Skin (dermis)	Macrophages, fibroblasts, keratinocytes	Fibroblasts, endothelial cells	TGFβ, EGF, VEGF, IGF	Early and late macrophages (similar to M1/M2)	Full-thickness wound scarring in adults	Excessive inflammation Decreased migration Collagen accumulation	IFN-α, IFN-β, IFN-γ; steroids
Heart	M1 or Ly-6C^hi monocytes/macrophages	Resident cardiomyocytes	n/a	Four pools of cardiac macrophages; sequential Ly6C^hi, Ly6C^lo	Myocardial infarction Heart failure	Lack of progenitors; Insufficient immune polarization	ACE inhibitors
Skeletal muscle	Macrophages and FAPs	Satellite cells	T_reg amphiregulin, IL-6, IL-1β, TNFα, IGF1, TGFβ	Muscle T_reg; M1/M2	Muscular dystrophy	Myofiber defect; satellite cell exhaustion; chronic inflammation	Glucocorticoids
CNS (myelination)	Macrophages and microglia	Oligodendrocyte progenitor cells	IGF1	M1/M2	Multiple sclerosis	Impaired clearance of myelin debris	anti-GM-CSF; Pioglitazone (PPARg agonist); Glatiramer acetate
Liver	Kupffer cell and liver macrophages	Hepatocytes and Hepatic Progenitor Cells	Eosinophil IL-4; Kupffer IL-6, TNFα	Inflammatory and restorative macrophages; T_h1, T_h2, T_h17 lymphocytes	Chronic liver disease (viral, toxic, autoimmune, metabolic)	Unresolved fibrosis	TLR4, CCR2 inhibitors; PPAR-α/β agonists
Bone	Osteoclast	Monocyte progenitor	Csf1	n/a	Osteopetrosis or osteoperosis	Lack of or excessive bone resorption	IFN-γ1b, corticosteroid; RANKL inhibitor (mAb)