Human Placentally-Derived Stem Cells Abrogate Fibrosis And Augment Lung Repair But Differ In Plasticity

Looking for the elusive lung stem cell niche

“…Finally, it must be noted that in order to fully exploit the different forms of stem cells we need a better understanding of organ morphogenesis. Further developments in developmental biology together with stem cell biology and tissue engineering hold the promise to ultimately transform regenerative medicine [ 9 ].…”

“…In the more distal lung, it has been studied that Clara cell population is restored by the proliferation and self-renewal of a small number of resistant or ‘variant’ (Clara v) cells after naphthalene injury. These are label-retaining subpopulations of Clara cells located adjacent to cluster of neuroendocrine bodies (NEBs) in the bronchioles [ 10 ] or at the broncho-alveolar duct junctions (BADJs), where there are very few neuroendocrinal bodies [ 9 , 10 , 36 ]. The lack of expression of cytochrome P450 on the Clara ‘variant’ may represent less differentiated Clara cells, when related to majority of Clara cell population.…”

“…In models of ablative radiation injury, CD45+ lung SP cells have demonstrated transient repopulation of the bone marrow and indicated that CD45+ lung SP cells are analogous to the short-term repopulating hematopoietic cell. In models of ablative radiation injury, CD45+ SP cells have been demonstrated to be sufficient for reconstitution of the bone marrow [ 9 , 32 ]. In addition, in one report, marked SP cells were shown to repopulate damaged lung [ 53 ] in irradiated mice, resulting in rare, but detectable, fibroblasts and alveolar and bronchial epithelial cells.…”

“…The cells within a tissue such as the lung where rapid turnover of cells is the rule where efficient regeneration need to balance the high level of oxidative wear and tear, we believe, in the light of the data presented in this paper, that identity of a cell, both structural and functional, undergo a dynamic plasticity by which they can change back and forth between functionally competent lineage restricted cells of the different anatomical tissue sub-types of the lung and progenitor-like cells that can differentiate and trans-differentiate into cells of the required type according to the current demand to restore homeostatsis in the lung [ 9 , 30 , 32 ]. To accomplish this there must be efficient and seamless de-differentiation and differentiation of the same cellular pool by simply switching on and off, certain defined molecular switches.…”