Adequate recovery of hematopoietic stem cell (HSC) niches after cytotoxic conditioning regimens is essential to successful bone marrow transplantation. Yet, very little is known about the mechanisms that drive the restoration of these niches after bone marrow injury. Here we describe a profound disruption of the marrow microenvironment after lethal total body irradiation of mice that leads to the generation of osteoblasts restoring the HSC niche, followed by a transient, reversible expansion of this niche. Within 48 hours after irradiation, surviving host megakaryocytes were observed close to the endosteal surface of trabecular bone rather than in their normal parasinusoidal site concomitant with an increased stromal-derived factor-1 level. A subsequent increase in 2 megakaryocyte-derived growth factors, platelet-derived growth factor-beta and basic fibroblast growth factor, induces a 2-fold expansion of the population of N-cadherin-/osteopontin-positive osteoblasts, relative to the homeostatic osteoblast population, and hence, increases the number of potential niches for HSC engraftment. After donor cell engraftment, this expanded microenvironment reverts to its homeostatic state. Our results demonstrate the rapid recovery of osteoblastic stem cell niches after marrow radioablation, provide critical insights into the associated mechanisms, and suggest novel means to manipulate the bone marrow microenvironment to promote HSC engraftment.

Restoration and reversible expansion of the osteoblastic hematopoietic stem cell niche after marrow radioablation / Dominici, Massimo; Rasini, Valeria; Bussolari, Rita; X., Chen; T. J., Hofmann; Spano, Maria Carlotta; D., Bernabei; Veronesi, Elena; F., Bertoni; Paolucci, Paolo; Conte, Pierfranco; E. M., Edwin. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 114:(2009), pp. 2333-2343.

Restoration and reversible expansion of the osteoblastic hematopoietic stem cell niche after marrow radioablation

DOMINICI, Massimo;RASINI, Valeria;BUSSOLARI, Rita;SPANO, Maria Carlotta;VERONESI, Elena;PAOLUCCI, Paolo;CONTE, Pierfranco;
2009

Abstract

Adequate recovery of hematopoietic stem cell (HSC) niches after cytotoxic conditioning regimens is essential to successful bone marrow transplantation. Yet, very little is known about the mechanisms that drive the restoration of these niches after bone marrow injury. Here we describe a profound disruption of the marrow microenvironment after lethal total body irradiation of mice that leads to the generation of osteoblasts restoring the HSC niche, followed by a transient, reversible expansion of this niche. Within 48 hours after irradiation, surviving host megakaryocytes were observed close to the endosteal surface of trabecular bone rather than in their normal parasinusoidal site concomitant with an increased stromal-derived factor-1 level. A subsequent increase in 2 megakaryocyte-derived growth factors, platelet-derived growth factor-beta and basic fibroblast growth factor, induces a 2-fold expansion of the population of N-cadherin-/osteopontin-positive osteoblasts, relative to the homeostatic osteoblast population, and hence, increases the number of potential niches for HSC engraftment. After donor cell engraftment, this expanded microenvironment reverts to its homeostatic state. Our results demonstrate the rapid recovery of osteoblastic stem cell niches after marrow radioablation, provide critical insights into the associated mechanisms, and suggest novel means to manipulate the bone marrow microenvironment to promote HSC engraftment.
114
2333
2343
Restoration and reversible expansion of the osteoblastic hematopoietic stem cell niche after marrow radioablation / Dominici, Massimo; Rasini, Valeria; Bussolari, Rita; X., Chen; T. J., Hofmann; Spano, Maria Carlotta; D., Bernabei; Veronesi, Elena; F., Bertoni; Paolucci, Paolo; Conte, Pierfranco; E. M., Edwin. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 114:(2009), pp. 2333-2343.
Dominici, Massimo; Rasini, Valeria; Bussolari, Rita; X., Chen; T. J., Hofmann; Spano, Maria Carlotta; D., Bernabei; Veronesi, Elena; F., Bertoni; Paolucci, Paolo; Conte, Pierfranco; E. M., Edwin
File in questo prodotto:
File Dimensione Formato  
Restoration.pdf

non disponibili

Tipologia: Post-print dell'autore (bozza post referaggio)
Dimensione 1.87 MB
Formato Adobe PDF
1.87 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/648728
Citazioni
  • ???jsp.display-item.citation.pmc??? 78
  • Scopus 151
  • ???jsp.display-item.citation.isi??? 146
social impact