BM-derived cells randomly contribute to neoplastic and non-neoplastic epithelial tissues at low rates

Abstract

Epithelial cancers can arise from BM-derived cells (BMCs) in animal models. We studied whether the same phenomenon can occur in humans. Biopsy specimens from carcinomas and healthy adjacent tissues were obtained from three women who had undergone allogeneic BMT from an HLA-matched brother. Complete donor hematopoietic chimerism was verified by cytogenetic analysis, RFLP analysis or by reverse transcription-PCR analysis. Biopsies were studied for the presence of the Y chromosome derived from BM-derived cells by combined FISH and immunohistochemical staining. In our studies, we showed that human epithelial neoplastic and adjacent nonneoplastic tissues incorporate the Y chromosome at low and comparable rates. The lack of enrichment in malignancies argues against the possibility that BMderived cells represent a direct source of carcinomas, and we suggest that these cells randomly contribute to neoplastic and non-neoplastic epithelial cells. On the basis of the absence of a fusion karyotype, we favor a model in which the differentiation of BM-derived cells is largely determined by the microenvironment encountered.

Microchimerism in Salivary Glands after Blood- and Marrow-Derived Stem Cell Transplantation

“…Other groups have suggested that microchimerism might contribute to the development of neoplastic epithelial tissues [18,19]. However, this remains unresolved as there are also data arguing against the possibility that BMDSCs represent a direct source of carcinomas in the recipients [20]. There are reports of better BMDSC donor cell engraftment at sites with injury, such as lung after radiation [6], GI inflammation [21], and skin blistering [16].…”

Stem cell transplantation for tetratricopeptide repeat domain 7A deficiency: long-term follow-up

“…[10][11][12][13] Moreover, evidence on the interaction between hematopoietic donor and host epithelial cells in stem cell transplantation might lead to a potential benefit of HSCT in certain epithelial disorders. [14][15][16] TTC7A-deficient patients with associated immunodeficiency may therefore benefit from HSCT; however, the effect of engrafted donor cells on chronic intestinal inflammation and gut epithelial tissue regeneration is unknown. 14,15 Follow-up data on HSCT in TTC7A deficiency are required to understand the impact of this treatment on the disease phenotype and to guide the management of future cases.…”

“…[14][15][16] TTC7A-deficient patients with associated immunodeficiency may therefore benefit from HSCT; however, the effect of engrafted donor cells on chronic intestinal inflammation and gut epithelial tissue regeneration is unknown. 14,15 Follow-up data on HSCT in TTC7A deficiency are required to understand the impact of this treatment on the disease phenotype and to guide the management of future cases. In this study, we report the clinical and histological evolution of 4 TTC7A-deficient patients who are alive 19 to 114 months post-HSCT.…”

“…6 Six published patients underwent HSCT, of whom 5 died within the first year postprocedure (3 from infections, 1 from disease progression, and 1 from unknown causes). 6,8,9,15 The only survivor is reported here as patient 4.…”

Plasticity after allogeneic hematopoietic stem cell transplantation

“…However, the conjecture about the cell origin of the non-hematopoietic tissues after HSCT has led to a closely related theory that cancer could also be donor-derived. So far, the evidence of this hypothesis is extremely scarce and only further systematic searches for donor-derived stem cells in the newly diagnosed solid tumor in long-term survivors after HSCT will shed some light on this controversial theory (Houghton et al, 2004;Alison et al, 2006;Arai et al, 2006;Avital et al, 2007;Soldini et al, 2008).…”