Germ cell tumors from adult bone marrow
While evaluating stem cell-based therapies in rodent stroke models, Dr. Burns and colleagues noticed that certain bone marrow-derived cell lines formed tumors after transplantation.
Further evaluation revealed embryonic yolk sac tumors in grafts derived from multipotent adult progenitor cells (MAPCs) expressing high levels of the transcription factor Oct4. MAPCs reproducibly resulted from spontaneous in vitro epigenetic reprograming of CD45-bone marrow stem cells to an embryonic hypoblast-like state with marked demethylation of the Oct4 promoter.
Interestingly, systemic delivery of the same cells in other mouse models yielded therapeutic effects without tumor formation, including restoring immune function in immune deficient mice. As such, these results caution that cells that appear safe in one setting could still misbehave in other settings, especially when cells are implanted at high density into a confined space. The Regenerative Neurosurgery and Neuro-Oncology Lab and colleagues continue driving efforts to establish standardized strategies that ensure the safety of adult-derived cells used for regenerative therapies.
- Serafini M, Dylla SJ, Oki M, Heremans Y, Jakub Tolar, Jiang Y, Buckley SM, Pelacho B, Burns TC, Frommer S, Rossi DJ, Bryder D, Panoskaltsis-Mortari A, O'Shaughnessy MJ, Nelson-Holte M, Fine GC, Weissman IL, Blazar BR, Verfaillie CM. Hematopoietic reconstitution by multipotent adult progenitor cells: Precursors to long-term hematopoietic stem cells. Journal of Experimental Medicine. 2007;204:129.
- Burns TC, Verfaillie CM, Low WC. Stem cells for ischemic brain injury: A critical review. Journal of Comparative Neurology. 2009; doi:10.1002/cne.22038.
- Nigro AL, Geraerts M, Notelaers T, Roobrouck VD, Muijtjens M, Eggermont K, Subramanian K, Ulloa-Montoya F, Park Y, Owens J, Burns TC, Low W, Sharma S, Sohni A, Crabbe A, Pauwelyn K, Roelandt P, Agirre X, Prosper F, O'Brien TD, Zwijsen A, Hu W, Binas B, Verfaillie CM. MAPC culture conditions support the derivation of cells with nascent hypoblast features from bone marrow and blastocysts. Journal of Molecular Cell Biology. 2012; doi:10.1093/jmcb/mjs046.
- Leten C, Roobrouck VD, Struys T, Burns TC, Dresselaers T, Velde GV, Santermans J, Lo Nigro A, Ibrahimi A, Gijsbers R, Eggermont K, Lambrichts I, Verfaillie CM, Himmelreich U. Controlling and monitoring stem cell safety in vivo in an experimental rodent model. Stem Cells. 2014; doi:10.1002/stem.1819.