Fetal cells home to injured mother tissue

The current accepted method of using cord blood is for post myeloablative hematopoietic reconstitution in patients with leukemias, or other hematological/metabolic disorders. Essentially the idea is that if you destroy the resident stem cells and administer "healthy" stem cells, then the progeny of the healthy stem cells will act in a dominant manner to reverse the disease.

Many clinicians, primarily, but not exclusively, outside of the United States have been using cord blood without any type of myeloablation. The rational for this approach is described in a paper published by the company Medistem. There are patents issued on non-myeloablative conditioning however these approaches still involve some type of immune suppression.

The rationale of why cord blood stem cells may have activity across allogeneic barriers, broadly speaking, can be broken down into 2 main possible methods of activity. The first, the cells may secrete growth factors and then be cleared away by the anti-allogeneic immune response. The second is that certain cells in the cord blood may be resistant to the allogeneic immune response. For example, CD34 cells are known, under certain conditions to exert a veto effect in terms of shutting down responding T cells. Similar effects have been ascribed to mesenchymal stem cells.

Since the fetal circulation is the source of cord blood, some are of the opinion that if allogeneic cord blood is to have an effect on a recipient in absence of immune suppression, then fetal cells should also be found in the mother.

While it is known that fetal cells do enter maternal circulation, the question is whether these cells have therapeutic effects or deleterious effects. For example, there are published associations between the number of fetal-derived cells in the mother and autoimmunity.

In a recent publication (O'Donoghue et al. Microchimeric fetal cells cluster at sites of tissue injury in lung decades after pregnancy. Reprod Biomed Online. 2008;16(3):382-390) this question was examined in detail.

The investigators harvested lung samples from women undergoing surgery for oncological purposes.

FISH was performed for Y chromosome in the samples.

Y-chromosome cells were seen in both the lung and thymus of all women who had male offspring but not in those who had female offspring.

The Y-chromosome cells were 7 fold higher in the lung and thymus compared to the bone marrow.

The Y-chromosome cells were selectively clustered around tumor tissue as compared to non-neoplastic lung tissues.

Are the cells helping the tumor by stimulating angiogenesis ? Are they acting as endogenous "healing cells"? While we do not know this, we do know that the cells have persisted, in some cases even for decades after the pregancy. Also of interest is the possibility that fetally derived cells contribute to shaping of the mother's immune system. Why else would so many of them be in the thymus? It is known that intrathymic injection of antigen induces tolerance.