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Self-Renewing Human Bone Marrow Mesenspheres Promote Hematopoietic Stem Cell Expansion

Isern, Joan ; Martin-Antonio, Beatriz ; Ghazanfari, Roshanak LU ; Martin, Ana M. ; Lopez, Juan A. ; del Toro, Raquel ; Sanchez-Aguilera, Abel ; Arranz, Lorena ; Martin-Perez, Daniel and Suarez-Lledo, Maria , et al. (2013) In Cell Reports 3(5). p.1714-1724
Abstract
Strategies for expanding hematopoietic stem cells (HSCs) include coculture with cells that recapitulate their natural microenvironment, such as bone marrow stromal stem/progenitor cells (BMSCs). Plastic-adherent BMSCs may be insufficient to preserve primitive HSCs. Here, we describe a method of isolating and culturing human BMSCs as nonadherent mesenchymal spheres. Human mesenspheres were derived from CD45(-) CD31(-) CD71(-) CD146(+) CD105(+) nestin(+) cells but could also be simply grown from fetal and adult BM CD45(-)-enriched cells. Human mesenspheres robustly differentiated into mesenchymal lineages. In culture conditions where they displayed a relatively undifferentiated phenotype, with decreased adherence to plastic and increased... (More)
Strategies for expanding hematopoietic stem cells (HSCs) include coculture with cells that recapitulate their natural microenvironment, such as bone marrow stromal stem/progenitor cells (BMSCs). Plastic-adherent BMSCs may be insufficient to preserve primitive HSCs. Here, we describe a method of isolating and culturing human BMSCs as nonadherent mesenchymal spheres. Human mesenspheres were derived from CD45(-) CD31(-) CD71(-) CD146(+) CD105(+) nestin(+) cells but could also be simply grown from fetal and adult BM CD45(-)-enriched cells. Human mesenspheres robustly differentiated into mesenchymal lineages. In culture conditions where they displayed a relatively undifferentiated phenotype, with decreased adherence to plastic and increased self-renewal, they promoted enhanced expansion of cord blood CD34(+) cells through secreted soluble factors. Expanded HSCs were serially transplantable in immunodeficient mice and significantly increased long-term human hematopoietic engraftment. These results pave the way for culture techniques that preserve the self-renewal of human BMSCs and their ability to support functional HSCs. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cell Reports
volume
3
issue
5
pages
1714 - 1724
publisher
Cell Press
external identifiers
  • wos:000321899300039
  • scopus:84878530991
ISSN
2211-1247
DOI
10.1016/j.celrep.2013.03.041
language
English
LU publication?
yes
id
2574fc55-4df6-42ff-9d64-fa7e269ba479 (old id 4050219)
date added to LUP
2016-04-01 13:55:10
date last changed
2025-10-14 13:18:50
@article{2574fc55-4df6-42ff-9d64-fa7e269ba479,
  abstract     = {{Strategies for expanding hematopoietic stem cells (HSCs) include coculture with cells that recapitulate their natural microenvironment, such as bone marrow stromal stem/progenitor cells (BMSCs). Plastic-adherent BMSCs may be insufficient to preserve primitive HSCs. Here, we describe a method of isolating and culturing human BMSCs as nonadherent mesenchymal spheres. Human mesenspheres were derived from CD45(-) CD31(-) CD71(-) CD146(+) CD105(+) nestin(+) cells but could also be simply grown from fetal and adult BM CD45(-)-enriched cells. Human mesenspheres robustly differentiated into mesenchymal lineages. In culture conditions where they displayed a relatively undifferentiated phenotype, with decreased adherence to plastic and increased self-renewal, they promoted enhanced expansion of cord blood CD34(+) cells through secreted soluble factors. Expanded HSCs were serially transplantable in immunodeficient mice and significantly increased long-term human hematopoietic engraftment. These results pave the way for culture techniques that preserve the self-renewal of human BMSCs and their ability to support functional HSCs.}},
  author       = {{Isern, Joan and Martin-Antonio, Beatriz and Ghazanfari, Roshanak and Martin, Ana M. and Lopez, Juan A. and del Toro, Raquel and Sanchez-Aguilera, Abel and Arranz, Lorena and Martin-Perez, Daniel and Suarez-Lledo, Maria and Marin, Pedro and Van Pel, Melissa and Fibbe, Willem E. and Vazquez, Jesus and Scheding, Stefan and Urbano-Ispizua, Alvaro and Mendez-Ferrer, Simon}},
  issn         = {{2211-1247}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{1714--1724}},
  publisher    = {{Cell Press}},
  series       = {{Cell Reports}},
  title        = {{Self-Renewing Human Bone Marrow Mesenspheres Promote Hematopoietic Stem Cell Expansion}},
  url          = {{https://lup.lub.lu.se/search/files/3663618/4281438.pdf}},
  doi          = {{10.1016/j.celrep.2013.03.041}},
  volume       = {{3}},
  year         = {{2013}},
}