The Current Hypothesis

Much has been told about the bone marrow microenvironment, which has been considered to have a significant physiological role to maintain the cellular balance in the periphery [37, 39, 40, 41, 70, 71]. The present concept of bone marrow "niche" [64] relates a more scientific concept in favour of cellular generation from pluripotent stem cells. The "niche theory" elaborated the intricate relationship in between the stem and stromal cells [72], their interdependence concerned over the network function with the cytokines, growth factors and the sequential maturation of the pluripotent cells towards healthy functional cells [41, 73]. Other observations provided the evidence for the involvement of matrix components in haemopoietic stem cell (HSC) regulation and further emphasize the importance of regulating anchorage and quiescence as essential features of "niche" function [74].

Investigations conducted in our laboratory both in experimentally induced 'Aplastic Anaemia' mice and in pesticide victims (patients) amply confirm the influence of microenvironmental association factor in the developmental and functional kinetics of stem cells in culture [28]. The observations showed that the association factors, which are the integral components of the niche as well, might influence the above functions. The cord blood derived plasma factors (CBPF) are the representative nourishing molecules for the stem cell development and function, as authenticated. These discussions provide ample evidences towards the fact that stem stromal interdependence is the basis of the spontaneous "self renewal system" of the stem cells and that the functional maturation are directed by the stromal secretions or by direct involvement for stem cell generation. In our laboratory we have been able to show that stromal involvement in terms of supporting base for stem cell generation or maintenance of stemness [75] and the stromal stimulation for stem cell generation in in-vitro culture are the pre- requisites of healthy bone marrow functions (Figure 3a, 3b, 3c).

A number of electron microscopic studies of in-vitro culture of bone marrow cells revealed the stromal cells as the parent supportive cells to the stem cell progeny representing the "niche" system (Figure 1b, 1c). Furthermore, evidences from the bone marrow of mice with experimentally induced Aplastic Anaemia showed series of stromal derangement (Figure 2b, 2c) together with distorted "niche" structure leading to deficient or no generation of stem cells. This might have an important bearing towards the initiation of bone marrow degenerative processes, wherein supplementation of stromal marrow microenvironment (stromal plus) can be a useful component for supportive therapy [29]. These need extensive and meticulous studies to confirm this speculation and reveal the actual scenario within the bone marrow.

Figure 3a. Ten days culture of pluripotent stem cells, isolated from the bone marrow of normal mice: shows microenvironmental coexistence of stromal cells, stromal precursors and pluripotent stem cells.

Figure 3b. Explant culture of stroma directed stem cell generation: interdependence of stem and stroma and stromal precursors is revealed on day ten.

Figure 3c. The stem stromal culture of bone marrow from Aplastic Anaemia induced mice: the inappropriate and deceased cellular kinetics is evidenced.

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