Role of bone marrow transplantation for correcting hemophilia A in mice

Antonia Follenzi, Sanj Raut, Simone Merlin, Rita Sarkar, Sanjeev Gupta

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

To better understand cellular basis of hemophilia, cell types capable of producing FVIII need to be identified. We determined whether bone marrow (BM)-derived cells would produce cells capable of synthesizing and releasing FVIII by transplanting healthy mouse BM into hemophilia A mice. To track donor-derived cells, we used genetic reporters. Use of multiple coagulation assays demonstrated whether FVIII produced by discrete cell populations would correct hemophilia A. We found that animals receiving healthyBMcells survived bleeding challenge with correction of hemophilia, although donor BM-derived hepatocytes or endothelial cells were extremely rare, and these cells did not account for therapeutic benefits. By contrast, donor BM-derived mononuclear and mesenchymal stromal cells were more abundant and expressed FVIII mRNAas well as FVIII protein. Moreover, injection of healthy mouse Kupffer cells (liver macrophage/mononuclear cells), which predominantly originate from BM, or of healthy BM-derived mesenchymal stromal cells, protected hemophilia A mice from bleeding challenge with appearance of FVIII in blood. Therefore, BM transplantation corrected hemophilia A through donor-derived mononuclear cells and mesenchymal stromal cells. These insights into FVIII synthesis and production in alternative cell types will advance studies of pathophysiological mechanisms and therapeutic development in hemophilia A.

Original languageEnglish (US)
Pages (from-to)5532-5542
Number of pages11
JournalBlood
Volume119
Issue number23
DOIs
StatePublished - Jun 7 2012

Fingerprint

Hemophilia A
Bone Marrow Transplantation
Bone
Bone Marrow
Mesenchymal Stromal Cells
Hemorrhage
Macrophages
Endothelial cells
Kupffer Cells
Coagulation
Liver
Assays
Bone Marrow Cells
Animals
Blood
Hepatocytes
Cells
Endothelial Cells
Injections
Therapeutics

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Role of bone marrow transplantation for correcting hemophilia A in mice. / Follenzi, Antonia; Raut, Sanj; Merlin, Simone; Sarkar, Rita; Gupta, Sanjeev.

In: Blood, Vol. 119, No. 23, 07.06.2012, p. 5532-5542.

Research output: Contribution to journalArticle

Follenzi, A, Raut, S, Merlin, S, Sarkar, R & Gupta, S 2012, 'Role of bone marrow transplantation for correcting hemophilia A in mice', Blood, vol. 119, no. 23, pp. 5532-5542. https://doi.org/10.1182/blood-2011-07-367680
Follenzi, Antonia ; Raut, Sanj ; Merlin, Simone ; Sarkar, Rita ; Gupta, Sanjeev. / Role of bone marrow transplantation for correcting hemophilia A in mice. In: Blood. 2012 ; Vol. 119, No. 23. pp. 5532-5542.
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