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 Blood, 12 November 2009, Vol. 114, No. 20, pp. 4566-4574.
Prepublished online as a Blood First Edition Paper on September 22, 2009; DOI 10.1182/blood-2009-03-209973.

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TRANSPLANTATION

Bone marrow as an alternative site for islet transplantation

Elisa Cantarelli1,*, Raffaella Melzi1,*, Alessia Mercalli1, Valeria Sordi1, Giuliana Ferrari2,3, Carsten Werner Lederer2, Emanuela Mrak4, Alessandro Rubinacci4, Maurilio Ponzoni5, Giovanni Sitia1, Luca G. Guidotti1,6, Ezio Bonifacio7, and Lorenzo Piemonti1

1 San Raffaele Diabetes Research Institute and 2 San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy; 3 Vita-Salute San Raffaele University, Milan, Italy; 4 Bone Metabolic Unit and 5 Pathology Unit, Unit of Lymphoid Malignancies, San Raffaele Scientific Institute, Milan, Italy; 6 Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, CA; and 7 Dresden University of Technology, Center for Regenerative Therapies Dresden, Dresden, Germany

The liver is the current site for pancreatic islet transplantation, but has many drawbacks due to immunologic and nonimmunologic factors. We asked whether pancreatic islets could be engrafted in the bone marrow (BM), an easily accessible and widely distributed transplant site that may lack the limitations seen in the liver. Syngeneic islets engrafted efficiently in the BM of C57BL/6 mice rendered diabetic by streptozocin treatment. For more than 1 year after transplantation, these animals showed parameters of glucose metabolism that were similar to those of nondiabetic mice. Islets in BM had a higher probability to reach euglycemia than islets in liver (2.4-fold increase, P = .02), showed a compact morphology with a conserved ratio between {alpha} and β cells, and affected bone structure only very marginally. Islets in BM did not compromise hematopoietic activity, even when it was strongly induced in response to a BM aplasia-inducing infection with lymphocytic choriomeningitis virus. In conclusion, BM is an attractive and safe alternative site for pancreatic islet transplantation. The results of our study open a research line with potentially significant clinical impact, not only for the treatment of diabetes, but also for other diseases amenable to treatment with cellular transplantation.


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