Moreover, although interesting studies showed that B cells are able to repopulate the plasma cell-deficient bone marrow [ 15], it remains rather unclear whether in autoimmunity LLPCs may be replenished from autoreactive memory B cells after therapeutic depletion of these cells.
Interestingly, these studies found no significant differences in outcomes with the use of less or more than the median number of transplanted stem cells; however, since most of the clinical trials used different cell isolation protocols and subsets of bone marrow-derived cells, it remains unclear which cell subpopulations would have the most beneficial effects [ 25].
Although certain thiazolidinedione derivatives can activate PPARγ and enhance bone marrow adiposity without altering BMD (34, 36), it remains plausible that adipocyte expansion may occur at the expense of bone in the absence of pharmaceutical intervention.
Given potential artifacts associated with irradiation-based lineage tracing, it remains unclear if bone-marrow-derived macrophages (BMDMs) are present in tumors of the brain, a tissue with no homeostatic involvement of BMDMs.
However, it remains unclear whether the bone marrow hosts ontogenically distinct MSCs in the same bones and whether they are endowed with specific functions.
It remains to be determined whether the bone marrow stem cells and progenitor cells recover to normal levels, or remain suppressed in Rad21 mutant mice.
It remains to be determined, however, whether contributions of bone marrow-derived cells or those of the parenchymal elements are primarily responsible for triggering the inflammatory changes and dictate the detrimental metabolic outcomes of obesity.
Although we used simvastatin in the present study, it remains uncertain which statin is most effective in suppressing PAI-1 secretion from bone marrow adipocytes.
It remains to be determined if the increase in epithelial-like progenitor population in bone marrow and peripheral blood is the cause or consequence of the epithelial hyperproliferation seen in CF, which, warrants further exploration.
Therefore, we can not exclude that the DL-101 epitope may be sensitive to freezing-thawing procedure and it remains interesting but not easy to verify the possibility of heterogeneity inside the bone marrow plasma cells.
