Depletion of reserve in the hemopoietic system: III. Factors affecting the serial transplantation of bone marrow.

The effects of serial transplantation on murine bone marrow were studied. Decline of CFUs content and the maximum number of successful transplantations possible were the criteria considered to indicate stem cell changes accompanying the serial transplants. Variables of experimentation included age of the marrow cell donors, addition of thymocytes to the transplanted marrow, differing time intervals between transplantations and differing numbers of donor marrow cells injected throughout a given transplant series. All of the transplantation series were monitored by karyotyping the marrow cells after each transplantation to document the continuance of the original donor cells. Reversions to recipient cell type did occur late in some series and were considered the end point of these series, as were the disappearance of CFUs and deaths of recipients due to transplant failure (the latter two always corresponded well). Only the donor marrow cell dose was found to be an important variable in the continuance of a transplant series and it was possible to obtain 8 successful serial transplantations with the highest marrow cell dose. All of the series given lower cell doses failed at the fifth or sixth transplant, regardless of other variables involved. A naturally occurring hierarchy of hemopoietic stem cells coupled with stem cell differentiative changes caused by extreme and repeated demands for population replenishment is offered as a probable reason for the results obtained, while other possibilities are discussed as well.