The additive effect of mesenchymal stem cells and bone morphogenetic protein 2 on γ-irradiated bone marrow in mice

Cell Biochem Biophys. 2011 Dec;61(3):539-50. doi: 10.1007/s12013-011-9236-y.

Abstract

Irradiation from γ-rays can cause severe damage to bone marrow and hematopoietic tissues. Presently, the most effective method available to treat severe hematopoietic injury is a bone marrow transplant (BMT). Allogeneic BMT is a difficult technique to perform due to the differences in human leukocyte antigen proteins between the donor and recipient, with acute graft-versus-host disease being a major complication of the technique. This limits the widespread applicability of allogeneic BMT. To develop a novel treatment for acute hematopoietic damage, we transplanted bone marrow derived mesenchymal stem cells (MSCs) into recipient mice and treated them with recombinant human bone morphogenetic protein 2 (rhBMP2) to investigate whether MSCs and rhBMP2 could additively promote the restoration of hematopoietic function. MSCs are vital components of the hematopoietic microenvironment that supports hematopoiesis, and bone morphogenic protein is a key factor in hematopoiesis. The 30-day survival rate as well as the numbers of nucleated cells, bone marrow colony-forming unit-granulocyte macrophages, spleen colony-forming units and peripheral blood cells were enumerated. The results showed that, after γ-irradiation and transplantation, MSCs and rhBMP2 additively promoted and improved hematopoietic restoration and function in vivo and in vitro. This additive effect of MSCs and rhBMP2 may one day provide a novel means of treating acute hematopoietic damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / drug effects
  • Adipocytes / radiation effects
  • Animals
  • Biomarkers / metabolism
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / radiation effects*
  • Bone Morphogenetic Protein 2 / pharmacology*
  • Cell Count
  • Chondrocytes / cytology
  • Chondrocytes / drug effects
  • Chondrocytes / radiation effects
  • Dose-Response Relationship, Radiation
  • Gamma Rays / adverse effects*
  • Granulocyte-Macrophage Progenitor Cells / metabolism
  • Hematopoiesis / drug effects
  • Hematopoiesis / radiation effects
  • Humans
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / radiation effects
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mice
  • Mice, Inbred BALB C
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Osteoblasts / radiation effects
  • Survival Analysis

Substances

  • Biomarkers
  • Bone Morphogenetic Protein 2