2013
DOI: 10.1182/blood-2012-08-447417
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Intrathymic progenitor cell transplantation across histocompatibility barriers results in the persistence of early thymic progenitors and T-cell differentiation

Abstract: Key Points A thymus with available stem-cell niches can support long-term renewal by resident hematopoietic progenitors. Intrathymic administration of semiallogeneic BM progenitors results in long-term T-cell reconstitution in the absence of conditioning.

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Cited by 10 publications
(12 citation statements)
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“…Other findings also strongly support continued translational studies for the development of IT -based HSC transplantation strategies including: (a) a significantly more rapid kinetics of T-cell reconstitution following IT as compared to IV administration of HSC and (b) long-term thymopoiesis by IT-injected precursors in nonconditioned recipients, even across histocompatibility barriers (Fig. 2) [23,41,57,[60][61][62]. It will therefore be important to determine the clinical settings in which an IT transplantation approach, potentially enhancing HSC differentiation to a T lineage fate, will improve short-as well as long-term patient outcome.…”
Section: Future Perspectivesmentioning
confidence: 82%
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“…Other findings also strongly support continued translational studies for the development of IT -based HSC transplantation strategies including: (a) a significantly more rapid kinetics of T-cell reconstitution following IT as compared to IV administration of HSC and (b) long-term thymopoiesis by IT-injected precursors in nonconditioned recipients, even across histocompatibility barriers (Fig. 2) [23,41,57,[60][61][62]. It will therefore be important to determine the clinical settings in which an IT transplantation approach, potentially enhancing HSC differentiation to a T lineage fate, will improve short-as well as long-term patient outcome.…”
Section: Future Perspectivesmentioning
confidence: 82%
“…It will be important to determine whether the administration of donor HSCs by a combined IV/IT approach will promote a robust and long-lasting donor-derived thymopoiesis with an efficient donor-derived differentiation of other blood lineage cells (right panel). derived thymic settling cells that normally seed the thymus [51], with the former harboring T, B, granulocyte-macrophage (GM), and megakaryocyte-erythroid potential [61]. Furthermore, it has recently been elegantly shown that thymusautonomous T-cell differentiation can be sustained in mice with combined mutations in Rag2 together with either c-Kit or cc [58,59].…”
Section: (B)mentioning
confidence: 99%
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“…Previous preclinical cell-therapy studies using ITI were performed in recipients with genetic T-cell deficiencies, requiring no thymic conditioning when administering syngeneic BM cells 12 and chemotherapy when administering allogeneic BM cells. 11 We were able to demonstrate that an immunocompetent recipient can easily be conditioned for ITI by using sublethal TBI or even less toxic thymic irradiation. Moreover, instead of using lineage-marker-negative BM, we established purified LSK cells, the equivalent of human CD34 1 HSPCs, as the cell source for this immunotherapy.…”
Section: Discussionmentioning
confidence: 88%
“…Consistent with previous studies, we found efficient and longlasting T-cell reconstitution in the settings of both syngeneic and allogeneic BMT ( Figure 3A-F) from intrathymically injected HSPCs. [10][11][12] Total thymic cellularity and splenic donor T-cell numbers were not significantly altered as a result of ITI of HSPCs. In some cases, it appeared that the generation of ITI-derived T cells of LSK donor origin occurred at the expense of BM donor-derived T cells (2 months after syngeneic BMT, Figure 3B; 6 months after allogeneic BMT, Figure 3H).…”
Section: Iti Of Hspcs Generates Long-lasting Donor T Cells After Bmtmentioning
confidence: 93%