Tolerance induction by hematopoietic cell transplantation: combined use of stem cells and progenitor cells. J Heart Lung Transplant 2011 May;30(5):507-14
Date
01/25/2011Pubmed ID
21256050DOI
10.1016/j.healun.2010.11.021Scopus ID
2-s2.0-79953788266 (requires institutional sign-in at Scopus site) 3 CitationsAbstract
BACKGROUND: Donor-specific hematopoietic cell transplantation (HCT) in the form of bone marrow transplantation has been long recognized experimentally as a means of inducing tolerance for subsequently transplanted organs. Clinical translation has been limited, however, due to HCT-associated complications. Unrelated myeloid progenitors (MP) can be administered simultaneously with hematopoietic stem cells (HSC). This reduces susceptibility to bacterial and fungal infections in neutropenic mice in laboratory studies. It is not known, however, if the addition of third-party MP interferes with tolerance induction.
METHODS: BALB/c (H-2d) mice were irradiated and reconstituted with 4,000 AKR (H-2k) HSC or with 4,000 AKR HSC combined with 10(5) FVB (H-2q) MP. After 2 months, the mice received skin grafts from these three strains or from an unrelated strain, C57BL/6 (H-2b). Composition and origin of hematopoietic cells was analyzed using flow cytometry.
RESULTS: Mice in both groups accepted all the host-type- and HSC-donor-matched grafts, and rejected unrelated grafts. Surprisingly, recipients of both HSC and MP also accepted MP-matched skin grafts (14 of 14), even with very low levels of MP-derived cells in circulation. The analysis revealed that, although most hematopoietic cells were derived from HSC donors, regulatory T cells were derived from both donors as well as the recipient.
CONCLUSION: The addition of third-party MP cells does not interfere with HCT-induced tolerance induction and, surprisingly, induces MP-specific tolerance.
Author List
Domen J, Sun L, Trapp K, Maghami N, Inagaki E, Li Y, Simpson P, Gandy KLAuthor
Pippa M. Simpson PhD Adjunct Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsFemale
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Models, Animal
Myeloid Progenitor Cells
Skin Transplantation
T-Lymphocytes, Regulatory
Transplantation Tolerance
Treatment Outcome