Bone marrow regeneration after local injury: a review.

This paper is focused on a mechanically depleted medullary cavity as an experimental model for analysis of marrow regenerative programs. Mesenchymal cells form the characteristic marrow stroma. Hemic cell regeneration can occur without immigrant hematopoietic stem cells, although such cells are known to contribute to later stages of repopulation. The formation and resorption of trabecular bone appears to be intimately related to the development of a sinusoidal matrix, perhaps by serving as a callus or supporting lattice and perhaps by providing a mechanism for distribution of stromal progenitors. Hematopoiesis is initiated in sites of active bone resorption. The interplay of events consequent to marrow removal is strikingly similar to that seen with heterotopic marrow implants. Because stromal stem cells, unlike hematopoietic stem cells, do not migrate from distant sites, marrow stroma is the limiting factor in recovery from localized injury. Stromal stem cells are fairly radiosensitive but are not as sensitive as hematopoietic stem cells. The apparent radioresistance of stromal elements in an intact marrow seems to be due to their very low turnover rate. Latent radiation damage can be readily unmasked by conditions that promote their proliferation. This no doubt accounts for the radiosensitivity of stroma in an evacuatedmore » femur or heterotopic implant in contrast to its continued functional integrity with similar irradiation of in situ marrow. Even in an intact marrow, however, exposures in the 1000 rad range can lead to slowly evolving hypocellularity associated with diminished blood flow. With higher doses, aplasia of the irradiated site becomes progressively more generalized. It remains to be seen whether this limiting condition is due to the loss of specific regulatory functions of stromal components or merely reflects sinusoidal damage. (auth)« less