Fingernail transplants?

This is the latest in a series of observations in humans who have undergone stem-cell transplantation (SCT) indicating that donor cells end up in nonhematopoietic tissues including the gut, buccal mucosa, liver, and possibly muscle. While the present study irrefutably demonstrates that donor DNA is incorporated into nails, we should be cautious in our interpretation of exactly what this means. Controversy surrounds whether and how SCT can reconstitute nonhematopoietic tissues. Techniques that use fluorescence in situ hybridization (FISH) to identify donor Y chromosomes in recipient tissues cannot reliably exclude contaminating hematopoietic cells overlying epithelial tissue, nor can they exclude the occurrence of fusion of hematopoiesis-derived nuclei in tetraploidal nonhematopoietic cells, and not all studies have been positive.¹  Unresolved in these human studies is whether donor cells in these tissues are derived from hematopoietic stem cells or other progenitors transferred in the graft. Transplanted mesenchymal stromal cells, for example, can home to many tissues. In the present study, the occurrence of donor DNA in such nonvascular appendages as nails seems to rule out contamination by blood cells. Furthermore, the investigators sought, but failed to find, HTLV-1 DNA in nails from patients with HTLV-1 leukemia-lymphoma, confirming that blood cells (or at least lymphocytes) do not contribute DNA to fingernails, despite the opportunity that the vascular nail bed might offer. Could the cells containing donor DNA represent tetraploidal recipient keratinocytes containing fused donor nuclei? Probably not in the 3 cases who had more than 50% donor DNA. Thus, we are left to conclude that, at least occasionally, entirely donor-derived nonhematopoietic cells can make a long-lasting contributions to nail keratinocytes in the recipient.

This study is too small to define the factors conducive to the engraftment of nonhematopoietic donor cells. Since myeloablative transplants cause nail loss, it seems likely that such transplantation regimens would provide greater opportunities for nail neogeneration by donor cells. Indeed, all the patients with identifiable donor DNA had myeloablative SCT. In contrast, acute and chronic GVHD (as tissue-damaging processes) did not appear to be a prerequisite for donor nail chimerism—some of the highest donor DNA contributions were in patients with grade 0-I acute and limited chronic GVHD. In 8 of the 9 patients positive for donor DNA, bone marrow was the donor-cell source—would peripheral blood transplants also contain nonhematopoietic progenitors?

What are the wider implications of this observation? Substitution of recipient tissues by donor cells might reduce GVHD in the chimeric tissue—indeed, none of the patients in this study had chronic GVHD affecting the nails. However, until more is known about the contributing cells and the conditions required for reconstructing the integument, tissue reconstruction from SCT is still some way off.