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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • Joan Isern
  • Beatriz Martin-Antonio
  • Roshanak Ghazanfari
  • Ana M. Martin
  • Juan A. Lopez
  • Raquel del Toro
  • Abel Sanchez-Aguilera
  • Lorena Arranz
  • Daniel Martin-Perez
  • Maria Suarez-Lledo
  • Pedro Marin
  • Melissa Van Pel
  • Willem E. Fibbe
  • Jesus Vazquez
  • Stefan Scheding
  • Alvaro Urbano-Ispizua
  • Simon Mendez-Ferrer
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cellbiologi
Originalspråkengelska
Sidor (från-till)1714-1724
TidskriftCell Reports
Volym3
Utgivningsnummer5
StatusPublished - 2013
PublikationskategoriForskning
Peer review utfördJa

Nedladdningar

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Relaterad forskningsoutput

Roshanak Ghazanfari, 2017, Lund: Lund University, Faculty of Medicine. 78 s.

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

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