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Temporal definition of haematopoietic stem cell niches in a large animal model of in utero stem cell transplantation
Author(s) -
Jeanblanc Christine,
Goodrich Angelina Daisy,
Colletti Evan,
Mokhtari Saloomeh,
Porada Christopher D.,
Zanjani Esmail D.,
AlmeidaPorada Graça
Publication year - 2014
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12870
Subject(s) - haematopoiesis , stem cell , transplantation , biology , ontogeny , niche , bone marrow , in utero , fetus , cd34 , immunology , microbiology and biotechnology , medicine , endocrinology , pregnancy , genetics , ecology
Summary The fetal sheep model has served as a biologically relevant and translational model to study in utero haematopoietic stem cell transplantation ( IUHSCT ), yet little is known about the ontogeny of the bone marrow ( BM ) niches in this model. Because the BM microenvironment plays a critical role in the outcome of haematopoietic engraftment, we have established the correlation between the fetal‐sheep and fetal‐human BM niche ontogeny, so that studies addressing the role of niche development at the time of IUHSCT could be accurately performed. Immunofluorescence confocal microscopic analysis of sheep fetal bone from gestational days (gd) 25–68 showed that the BM microenvironment commences development with formation of the vascular niche between 25 and 36 gd in sheep; correlating with the events at 10–11 gestational weeks (gw) in humans. Subsequently, between 45 and 51 gd in sheep ( c . 14 gw in humans), the osteoblastic/endosteal niche started developing, the presence of CD 34 + CD 45 + cells were promptly detected, and their number increased with gestational age. IUHSCT , performed in sheep at 45 and 65 gd, showed significant haematopoietic engraftment only at the later time point, indicating that a fully functional BM microenvironment improved engraftment. These studies show that sheep niche ontogeny closely parallels human, validating this model for investigating niche influence/manipulation in IUHSCT engraftment.