Engraftability of Murine Bone Marrow-Derived Multipotent Mesenchymal Stem Cell Subpopulations in the Tissues of Developing Mice following Systemic Transplantation

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Abstract

Introduction: Cell therapies for generalized musculoskeletal diseases would require distribution of cells to all the skeletal tissues; however, there are controversies regarding the transplantability of multipotent mesenchymal stems cells (MSCs). We generated single-cell subpopulations of MSCs from murine bone marrow and assessed them for differences in trafficking through the circulatory system and engraftment in bone and other tissues. Materials and Methods: Seven single-cell clonal subpopulations were generated by serial dilution of GFP-marked MSCs isolated from bone marrow. The subpopulations were examined for putative MSC surface marker expression, in vitro differentiation toward osteogenic and adipogenic lineages, migration and engraftment in different tissues following intravenous delivery in normal, sublethally irradiated neonatal mice. Results: The surface marker expression profile revealed notable differences among clonal cells, specifically CD44 and CD105. All the cell subpopulations differentiated toward osteogenic and adipogenic lineages, with some committed to only one or the other. Two clones enriched in CXCR4 expression were highly efficient in migrating and engrafting in skeletal tissue including bone; this confirmed the role of this chemokine in cell migration. Donor cells retrieved from various tissues displayed different morphologies and potential differentiation into tissue cell type of engraftment, suggesting modification by the tissues in which the donor cells engrafted. Conclusion: We have reported that, within bone marrow, there are heterogeneous subpopulations of MSCs that may differ in their ability to migrate in the circulatory system and engraft in different tissues.

Original languageEnglish (US)
Pages (from-to)14-25
Number of pages12
JournalCells Tissues Organs
Volume201
Issue number1
DOIs
StatePublished - Dec 1 2015

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Multipotent Stem Cells
Mesenchymal Stromal Cells
Transplantation
Bone Marrow
Cardiovascular System
Musculoskeletal Diseases
Bone and Bones
Cell- and Tissue-Based Therapy
Chemokines
Cell Movement
Clone Cells

All Science Journal Classification (ASJC) codes

  • Anatomy
  • Histology

Cite this

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title = "Engraftability of Murine Bone Marrow-Derived Multipotent Mesenchymal Stem Cell Subpopulations in the Tissues of Developing Mice following Systemic Transplantation",
abstract = "Introduction: Cell therapies for generalized musculoskeletal diseases would require distribution of cells to all the skeletal tissues; however, there are controversies regarding the transplantability of multipotent mesenchymal stems cells (MSCs). We generated single-cell subpopulations of MSCs from murine bone marrow and assessed them for differences in trafficking through the circulatory system and engraftment in bone and other tissues. Materials and Methods: Seven single-cell clonal subpopulations were generated by serial dilution of GFP-marked MSCs isolated from bone marrow. The subpopulations were examined for putative MSC surface marker expression, in vitro differentiation toward osteogenic and adipogenic lineages, migration and engraftment in different tissues following intravenous delivery in normal, sublethally irradiated neonatal mice. Results: The surface marker expression profile revealed notable differences among clonal cells, specifically CD44 and CD105. All the cell subpopulations differentiated toward osteogenic and adipogenic lineages, with some committed to only one or the other. Two clones enriched in CXCR4 expression were highly efficient in migrating and engrafting in skeletal tissue including bone; this confirmed the role of this chemokine in cell migration. Donor cells retrieved from various tissues displayed different morphologies and potential differentiation into tissue cell type of engraftment, suggesting modification by the tissues in which the donor cells engrafted. Conclusion: We have reported that, within bone marrow, there are heterogeneous subpopulations of MSCs that may differ in their ability to migrate in the circulatory system and engraft in different tissues.",
author = "Feng Li and Christopher Niyibizi",
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N2 - Introduction: Cell therapies for generalized musculoskeletal diseases would require distribution of cells to all the skeletal tissues; however, there are controversies regarding the transplantability of multipotent mesenchymal stems cells (MSCs). We generated single-cell subpopulations of MSCs from murine bone marrow and assessed them for differences in trafficking through the circulatory system and engraftment in bone and other tissues. Materials and Methods: Seven single-cell clonal subpopulations were generated by serial dilution of GFP-marked MSCs isolated from bone marrow. The subpopulations were examined for putative MSC surface marker expression, in vitro differentiation toward osteogenic and adipogenic lineages, migration and engraftment in different tissues following intravenous delivery in normal, sublethally irradiated neonatal mice. Results: The surface marker expression profile revealed notable differences among clonal cells, specifically CD44 and CD105. All the cell subpopulations differentiated toward osteogenic and adipogenic lineages, with some committed to only one or the other. Two clones enriched in CXCR4 expression were highly efficient in migrating and engrafting in skeletal tissue including bone; this confirmed the role of this chemokine in cell migration. Donor cells retrieved from various tissues displayed different morphologies and potential differentiation into tissue cell type of engraftment, suggesting modification by the tissues in which the donor cells engrafted. Conclusion: We have reported that, within bone marrow, there are heterogeneous subpopulations of MSCs that may differ in their ability to migrate in the circulatory system and engraft in different tissues.

AB - Introduction: Cell therapies for generalized musculoskeletal diseases would require distribution of cells to all the skeletal tissues; however, there are controversies regarding the transplantability of multipotent mesenchymal stems cells (MSCs). We generated single-cell subpopulations of MSCs from murine bone marrow and assessed them for differences in trafficking through the circulatory system and engraftment in bone and other tissues. Materials and Methods: Seven single-cell clonal subpopulations were generated by serial dilution of GFP-marked MSCs isolated from bone marrow. The subpopulations were examined for putative MSC surface marker expression, in vitro differentiation toward osteogenic and adipogenic lineages, migration and engraftment in different tissues following intravenous delivery in normal, sublethally irradiated neonatal mice. Results: The surface marker expression profile revealed notable differences among clonal cells, specifically CD44 and CD105. All the cell subpopulations differentiated toward osteogenic and adipogenic lineages, with some committed to only one or the other. Two clones enriched in CXCR4 expression were highly efficient in migrating and engrafting in skeletal tissue including bone; this confirmed the role of this chemokine in cell migration. Donor cells retrieved from various tissues displayed different morphologies and potential differentiation into tissue cell type of engraftment, suggesting modification by the tissues in which the donor cells engrafted. Conclusion: We have reported that, within bone marrow, there are heterogeneous subpopulations of MSCs that may differ in their ability to migrate in the circulatory system and engraft in different tissues.

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