Recent progress on tissue-resident adult stem cell biology and their therapeutic implications

Abstract

Recent progress in the field of the stem cell research has given new hopes to treat and even cure diverse degenerative disorders and incurable diseases in human. Particularly, the identification of a rare population of adult stem cells in the most tissues/organs in human has emerged as an attractive source of multipotent stem/progenitor cells for cell replacement-based therapies and tissue engineering in regenerative medicine. The tissue-resident adult stem/progenitor cells offer the possibility to stimulate their in vivo differentiation or to use their ex vivo expanded progenies for cell replacement-based therapies with multiple applications in human. Among the human diseases that could be treated by the stem cell-based therapies, there are hematopoietic and immune disorders, multiple degenerative disorders, such as Parkinson's and Alzheimer's diseases, type 1 or 2 diabetes mellitus as well as eye, liver, lung, skin and cardiovascular disorders and aggressive and metastatic cancers. In addition, the genetically-modified adult stem/progenitor cells could also be used as delivery system for expressing the therapeutic molecules in specific damaged areas of different tissues. Recent advances in cancer stem/progenitor cell research also offer the possibility to targeting these undifferentiated and malignant cells that provide critical functions in cancer initiation and progression and disease relapse for treating the patients diagnosed with the advanced and metastatic cancers which remain incurable in the clinics with the current therapies.

Fig. 1

Scheme showing the possible molecular events and cellular changes associated with the development of vascular disorders and the potent cellular and gene therapies for restoring the damaged walls of blood vessels. The recruitment of smooth muscle cells (SMCs) which may participate to the vascular disorder formation by the release of extracellular matrix components such as collagen and fibronectin and immune cells including macrophage in injury area is shown. The stem cell-based therapy using genetically-modified stem/progenitor cells or BM-derived stem/progenitor cell transplant is also illustrated. ADSCs, adipose tissue-derived stem cells; CSCs, cardiac stem cells; EPCs, endothelial progenitor cells; HSCs, hematopoietic stem cells; MDSCs, muscle-derived stem cells; MSCs, mesenchymal stem cells

Fig. 2

Scheme showing the anatomic localization of the neural stem/progenitor cells and their putative niches in human adult brain as well as their malignant transformation into brain tumor stem/progenitor cells. The disorders that could be treated by stem cell-based and targeting therapies are indicated. BTSCs, brain tumor stem cells; NSCs, neural stem/progenitor cells

Fig. 3

Schematic structure of human eye showing the stem/progenitor cell localization in conjunctival, limbal and corneal epitheliums and retina as well as the disorders that could be treated by stem cell-based therapies. The corneal epithelial stem cells (CESCs) located in basal layer of the limbal epithelium and the migration of early and late transit-amplifying (TA) cells from limbus to the corneal basal cell layer during corneal epithelium regeneration is also illustrated. RSCs, retinal stem cells

Fig. 4

Scheme showing the anatomic localization of the adult stem/progenitor cells and their putative niches in epithelium lining the gastrointestinal tract, hepatic ductules and Hering’s canal and pancreatic duct epithelium. The disorders that could be treated by stem cell-based therapies are indicated. HOCs, hepatic oval cells; PSCs, pancreatic stem/progenitor cells