Drug targeting of adult stem cells has been proposed as a strategy for regenerative medicine, but very few drugs are known to target stem cell populations in vivo. Mesenchymal stem/progenitor cells (MSCs) are a multipotent population of cells that can differentiate into muscle, bone, fat, and other cell types in context-specific manners. Bortezomib (Bzb) is a clinically available proteasome inhibitor used in the treatment of multiple myeloma. Here, we show that Bzb induces MSCs to preferentially undergo osteoblastic differentiation, in part by modulation of the bone-specifying transcription factor runt-related transcription factor 2 (Runx-2) in mice. Mice implanted with MSCs showed increased ectopic ossicle and bone formation when recipients received low doses of Bzb. Furthermore, this treatment increased bone formation and rescued bone loss in a mouse model of osteoporosis. Thus, we show that a tissue-resident adult stem cell population in vivo can be pharmacologically modified to promote a regenerative function in adult animals.
Pharmacologic targeting of a stem/progenitor population in vivo is associated with enhanced bone regeneration in mice / S., Mukherjee; N., Raje; J. A., Schoonmaker; J. C., Liu; T., Hideshima; M. N., Wein; D. C., Jones; S., Vallet; M. L., Bouxsein; Pozzi, Samantha; S., Chhetri; Y. D., Seo; J. P., Aronson; C., Patel; M. T., Fulciniti; L. E., Purton; L. H., Glimcher; J. B., Lian; G., Stein; K. C., Anderson; D. T., Scadden. - In: THE JOURNAL OF CLINICAL INVESTIGATION. - ISSN 0021-9738. - ELETTRONICO. - 118:2(2008), pp. 491-504. [10.1172/JCI33102]
Pharmacologic targeting of a stem/progenitor population in vivo is associated with enhanced bone regeneration in mice
POZZI, Samantha;
2008
Abstract
Drug targeting of adult stem cells has been proposed as a strategy for regenerative medicine, but very few drugs are known to target stem cell populations in vivo. Mesenchymal stem/progenitor cells (MSCs) are a multipotent population of cells that can differentiate into muscle, bone, fat, and other cell types in context-specific manners. Bortezomib (Bzb) is a clinically available proteasome inhibitor used in the treatment of multiple myeloma. Here, we show that Bzb induces MSCs to preferentially undergo osteoblastic differentiation, in part by modulation of the bone-specifying transcription factor runt-related transcription factor 2 (Runx-2) in mice. Mice implanted with MSCs showed increased ectopic ossicle and bone formation when recipients received low doses of Bzb. Furthermore, this treatment increased bone formation and rescued bone loss in a mouse model of osteoporosis. Thus, we show that a tissue-resident adult stem cell population in vivo can be pharmacologically modified to promote a regenerative function in adult animals.
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