Biomedical Engineering Reference
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FIGURE 2.3 Stem cell biogenesis. (a) Embryonic stem cells, derived from the inner mass of
the blastocysts, are pluripotent cells that may differentiate toward all cell types. (b) Induced
pluripotent stem cells generated in vitro from somatic cells overexpressing Oct3/4, Sox2,
c-Myc, and Klf4. (c) ASCs are created during ontogeny (e.g., bone marrowmesenchymal stem
cells) and persist within the niche in most adult animal tissues and organs. Reproduced with
permission from Ref. [44].
2.3.1 Mesenchymal Stem Cells
The term mesenchymal stem cells (MSCs) was used by Caplan in 1991 to describe
the adherent cells derived from bone marrow that were capable of self-proliferation
as well as differentiation into different lineages of connective tissue. 25 However, the
identification of these cells dates back to 1867, when Cohnheim identified these cells
as nonhematopoietic cells. Traditionally, MSCs were thought to reside in both blood
and bone marrow. 26 However, recent researches provide evidence of MSCs in diverse
tissue and organs such as lung, adipose tissues, amniotic fluid, umbilical cord,
periosteum, dental pulp, hair follicle, thymus, and trabecular bone. 27,28 MSCs give
rise to connective tissues of various origin such as bone (osteogenic), cartilage
(chondrogenic), and fat (adipogenic). 29 MSCs are also worthy of giving rise to
several other tissues of mesodermal (myocyte, osteocyte, endothelium, cardiomyo-
cyte), ectodermal (neuronal), and endodermal (hepatic, pancreatic, respiratory
epithelium) lineages. 30 MSCs constitute approximately 2-3% of the total nuclear
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