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Barbieri Thesis - BioMedical Materials program (BMM)

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Chapter 1 – Introduction<br />

phenotype and de–differentiate into blastemal cells. Such de–differentiated cells then<br />

proliferate and later differentiate again into phenotypes capable to synthesize the<br />

needed tissues eventually regenerating the whole amputated body parts.<br />

Salamanders can regenerate, besides legs and tail, also injured retina and<br />

intestine. [52, 59] Being unable of blastema formation (i.e. the source of cells for<br />

regeneration), larger animals including human beings lost much of their regenerative<br />

potential. [80] In mammals one of the most exciting example of natural tissue<br />

regeneration is given by the liver, which fully regenerates itself when resected. This<br />

process is initiated by the tissue removal, when all cells comprising the left intact<br />

organ are triggered to proliferate until the reconstruction of the missing parts. [81]<br />

Table 1. Overview of stem cells in various body tissues.<br />

Tissue / organ Description<br />

Bone marrow contains two kinds of somatic stem cells, namely<br />

hematopoietic stem cells (HSCs)<br />

Bone marrow<br />

[60] and marrow stromal cells (MSCs, called<br />

also mesenchymal stem cells). [61, 62] HSCs are capable to differentiate into all<br />

blood lineages and can regenerate bone marrow after loss. [60, 63, 64] MSCs<br />

can differentiate into various cellular phenotypes according to the tissue they<br />

migrate, e.g. chondrocytes if they move to cartilage tissue, osteoblasts if in<br />

bone, myoblasts if in muscle. Besides these, they can generate also<br />

adipocytes and endothelial cells. MSCs move to injured tissues and<br />

participate to their repair or regeneration, but they appear having no role in<br />

tissue homeostasis. [61, 62, 65–67] It has recently been proposed to use MSCs<br />

even for lung diseases treatment. [68]<br />

Liver contains stem and progenitor cells that generate oval cells, which then<br />

Liver<br />

differentiate into hepatocytes and biliary cells. [69, 70]<br />

Neural stem cells (NSCs) allow neurogenesis by giving rise to neurons,<br />

astrocytes and oligodendrocytes.<br />

Brain<br />

[43, 71, 72] However, it is still not clear whether<br />

newly formed neurons in adult brain are integrated into its neural circuits and<br />

thus the purpose of neurogenesis is under debate. [73]<br />

The epidermis has a high renewal rate (~3–4 weeks) because of its<br />

exposure to the extra–body environment and thus it has to cope with various<br />

stresses, such as exposure to sunlight and substances or friction. Three skin<br />

Skin<br />

sites for stem cells have been identified in the epidermis, particularly in<br />

interfollicular area, hair follicle bulge and sebaceous glands. The stem cells<br />

lying in the hair follicle bulge participate to the regeneration of surface<br />

epidermal cells after skin injury. [74, 75]<br />

The small intestine hosts stem cells able to regenerate its crypts within few<br />

Intestinal epithelium<br />

Skeletal and<br />

cardiac muscle<br />

days. [76]<br />

Skeletal muscle myocytes never proliferate. Regeneration of injured skeletal<br />

muscle is assured by satellite cells localized beneath the myocyte basal<br />

lamina, which can differentiate into myocytes when triggered by injury. [77]<br />

The presence of stem cells in myocardium is still nowadays debated and it is<br />

proposed that heart may have progenitor cells having capacity to regenerate<br />

myocardium after small injuries, and that this ability decreases with aging. [78]<br />

Cornea The transparency of cornea is maintained by limbal stem cells (LSCs). [79]<br />

8

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