Impact of interactions of cellular components of the bone marrow microenvironment on hematopoietic stem and progenitor cell function

Brahmananda R. Chitteti, Ying Hua Cheng, Bradley Poteat, Sonia Rodriguez-Rodriguez, W. Goebel, Nadia Carlesso, Melissa Kacena, Edward Srour

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

Hematopoietic stem (HSC) and progenitor (HPC) cell fate is governed by intrinsic and extrinsic parameters. We examined the impact of hematopoietic niche elements on HSC and HPC function by analyzing the combined effect of osteoblasts (OBs) and stromal cells (SCs) on Lineage-Sca-1 +CD117+ (LSK) cells. CFU expansion and marrow repopulating potential of cultured Lineage-Sca-1+CD117+ cells were significantly higher in OB compared with SC cultures, thus corroborating the importance of OBs in the competence of the hematopoietic niche. OB-mediated enhancement of HSC and HPC function was reduced in cocultures of OBs and SCs, suggesting that SCs suppressed the OB-mediated hematopoiesis-enhancing activity. Although the suppressive effect of SC was mediated by adipocytes, probably through up-regulation of neuropilin-1, the OB-mediated enhanced hematopoiesis function was elaborated through Notch signaling. Expression of Notch 2, Jagged 1 and 2, Delta 1 and 4, Hes 1 and 5, and Deltex was increased in OB cultures and suppressed in SC and OB/SC cultures. Phenotypic fractionation of OBs did not segregate the hematopoiesis-enhancing activity but demonstrated that this function is common to OBs from different anatomic sites. These data illustrate that OBs promote in vitro maintenance of hematopoietic functions, including repopulating potential by up-regulating Notch-mediated signaling between HSCs and OBs.

Original languageEnglish
Pages (from-to)3239-3248
Number of pages10
JournalBlood
Volume115
Issue number16
DOIs
StatePublished - Apr 22 2010

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Osteoblasts
Hematopoietic Stem Cells
Bone
Bone Marrow
Stromal Cells
Hematopoiesis
Cell culture
Cell Culture Techniques
Neuropilin-1
Cell Lineage
Fractionation
Coculture Techniques
Adipocytes
Mental Competency
Up-Regulation
Stem Cells
Maintenance

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Impact of interactions of cellular components of the bone marrow microenvironment on hematopoietic stem and progenitor cell function. / Chitteti, Brahmananda R.; Cheng, Ying Hua; Poteat, Bradley; Rodriguez-Rodriguez, Sonia; Goebel, W.; Carlesso, Nadia; Kacena, Melissa; Srour, Edward.

In: Blood, Vol. 115, No. 16, 22.04.2010, p. 3239-3248.

Research output: Contribution to journalArticle

Chitteti, Brahmananda R. ; Cheng, Ying Hua ; Poteat, Bradley ; Rodriguez-Rodriguez, Sonia ; Goebel, W. ; Carlesso, Nadia ; Kacena, Melissa ; Srour, Edward. / Impact of interactions of cellular components of the bone marrow microenvironment on hematopoietic stem and progenitor cell function. In: Blood. 2010 ; Vol. 115, No. 16. pp. 3239-3248.
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