Self-Renewing Human Bone Marrow Mesenspheres Promote Hematopoietic Stem Cell Expansion
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4050219
- author
- organization
- publishing date
- 2013
- 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
- 2022-08-14 08:30:43
@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}}, }