Engraftment of quiescent progenitors and conversion to full chimerism after nonmyelosuppressive conditioning and hematopoietic cell transplantation in miniature swine

Brian Lima, Zachary L. Gleit, Andrew M Cameron, Sharon Germana, Michael C. Murphy, Robert Consorti, Qing Chang, Julian D. Down, Christian LeGuern, David H. Sachs, Christene A. Huang

Research output: Contribution to journalArticle

Abstract

Our laboratory has previously reported a nonmyelosuppressive preparative regimen for hematopoietic cell transplantation that leads to mixed chimerism and allograft tolerance in miniature swine across minor and major histocompatibility disparities. Stable chimerism persisted in most of these animals but was restricted to T cells and confined to peripheral blood. Because of the importance of myeloid and erythroid progenitors for the treatment of hematologic disorders, the objective of this study was to assess whether such cells existed in the bone marrow of these lymphoid chimeras as an indication of functional engraftment. Colony-formation assays were performed on donor inocula before infusion and on bone marrow cells harvested from the transplant recipients. Donor-origin myeloid/erythroid progenitor colonies were detected in bone marrow from 6 of 7 lymphoid chimeric recipients. A delayed donor leukocyte infusion successfully converted a stable lymphoid chimera to full multilineage chimerism within 2 weeks. Donor-origin myeloid/erythroid progenitors could be detected in the bone marrow of a host-matched recipient after myeloablation and adoptive transfer of mobilized cells from one of the engrafted lymphoid chimeras. These data suggest that even when only lymphoid chimerism is readily detected by flow cytometry, dormant myeloid/erythroid progenitors can exist and subsequent conversion to full donor chimerism can be achieved. The ability to establish multilineage engraftment and chimerism without significant toxicity may have important clinical implications for the management of nonmalignant hematopoietic disorders and hematologic malignancies.

Original languageEnglish (US)
Pages (from-to)571-582
Number of pages12
JournalBiology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
Volume9
Issue number9
DOIs
StatePublished - Sep 2003
Externally publishedYes

Fingerprint

Miniature Swine
Chimerism
Cell Transplantation
Tissue Donors
Bone Marrow
Hematologic Neoplasms
Transplantation Tolerance
Histocompatibility
Adoptive Transfer
Bone Marrow Cells
Flow Cytometry
Leukocytes
T-Lymphocytes
Transplants

Keywords

  • Bone marrow transplantation
  • Cytokine-mobilized peripheral blood
  • Miniature swine
  • Mixed chimerism

ASJC Scopus subject areas

  • Transplantation

Cite this

Engraftment of quiescent progenitors and conversion to full chimerism after nonmyelosuppressive conditioning and hematopoietic cell transplantation in miniature swine. / Lima, Brian; Gleit, Zachary L.; Cameron, Andrew M; Germana, Sharon; Murphy, Michael C.; Consorti, Robert; Chang, Qing; Down, Julian D.; LeGuern, Christian; Sachs, David H.; Huang, Christene A.

In: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, Vol. 9, No. 9, 09.2003, p. 571-582.

Research output: Contribution to journalArticle

Lima, Brian ; Gleit, Zachary L. ; Cameron, Andrew M ; Germana, Sharon ; Murphy, Michael C. ; Consorti, Robert ; Chang, Qing ; Down, Julian D. ; LeGuern, Christian ; Sachs, David H. ; Huang, Christene A. / Engraftment of quiescent progenitors and conversion to full chimerism after nonmyelosuppressive conditioning and hematopoietic cell transplantation in miniature swine. In: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2003 ; Vol. 9, No. 9. pp. 571-582.
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AU - Gleit, Zachary L.

AU - Cameron, Andrew M

AU - Germana, Sharon

AU - Murphy, Michael C.

AU - Consorti, Robert

AU - Chang, Qing

AU - Down, Julian D.

AU - LeGuern, Christian

AU - Sachs, David H.

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AB - Our laboratory has previously reported a nonmyelosuppressive preparative regimen for hematopoietic cell transplantation that leads to mixed chimerism and allograft tolerance in miniature swine across minor and major histocompatibility disparities. Stable chimerism persisted in most of these animals but was restricted to T cells and confined to peripheral blood. Because of the importance of myeloid and erythroid progenitors for the treatment of hematologic disorders, the objective of this study was to assess whether such cells existed in the bone marrow of these lymphoid chimeras as an indication of functional engraftment. Colony-formation assays were performed on donor inocula before infusion and on bone marrow cells harvested from the transplant recipients. Donor-origin myeloid/erythroid progenitor colonies were detected in bone marrow from 6 of 7 lymphoid chimeric recipients. A delayed donor leukocyte infusion successfully converted a stable lymphoid chimera to full multilineage chimerism within 2 weeks. Donor-origin myeloid/erythroid progenitors could be detected in the bone marrow of a host-matched recipient after myeloablation and adoptive transfer of mobilized cells from one of the engrafted lymphoid chimeras. These data suggest that even when only lymphoid chimerism is readily detected by flow cytometry, dormant myeloid/erythroid progenitors can exist and subsequent conversion to full donor chimerism can be achieved. The ability to establish multilineage engraftment and chimerism without significant toxicity may have important clinical implications for the management of nonmalignant hematopoietic disorders and hematologic malignancies.

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