Secretion of angiogenic proteins by human multipotent mesenchymal stromal cells and their clinical potential in the treatment of avascular osteonecrosis
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Secretion of angiogenic proteins by human multipotent mesenchymal stromal cells and their clinical potential in the treatment of avascular osteonecrosis. / Müller, I; Vaegler, M; Holzwarth, C; Tzaribatchev, N; Pfister, S M; Schütt, B; Reize, P; Greil, J; Handgretinger, R; Rudert, M.
In: LEUKEMIA, Vol. 22, No. 11, 11.2008, p. 2054-61.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Secretion of angiogenic proteins by human multipotent mesenchymal stromal cells and their clinical potential in the treatment of avascular osteonecrosis
AU - Müller, I
AU - Vaegler, M
AU - Holzwarth, C
AU - Tzaribatchev, N
AU - Pfister, S M
AU - Schütt, B
AU - Reize, P
AU - Greil, J
AU - Handgretinger, R
AU - Rudert, M
PY - 2008/11
Y1 - 2008/11
N2 - Osteonecrosis is a frequent complication after treatment for childhood leukemia and other steroid-based therapies. The success rate of core decompression surgery is limited. Therefore, we evaluated relevant biological characteristics of human multipotent mesenchymal stromal cells (MSCs) in vitro. MSCs cultured under low-oxygen tensions showed decreased proliferation and differentiation into bone. However, these MSCs secreted significant amounts of vascular endothelial-derived factor in the presence of interferon-gamma. These in vitro results with potential effects on neovascularization and bone regeneration as well as findings in animal models prompted us to treat five patients with steroid-induced osteonecrosis of the femur by core decompression surgery and instillation of expanded autologous MSCs. Within 3 weeks of culture, sufficient numbers of MSCs were generated using animal protein-free culture conditions. No chromosomal aberrations were detected by matrix-based comparative genomic hybridization. Application of MSCs during core decompression was feasible and safe. Median follow-up is 16 months and the patients in this pilot study reported clinical improvement. Formation of mineralized bone in the osteonecrotic cavity was proven by computed tomography. Taken together, MSCs display biological properties that may add to the efficiency of surgical treatment in osteonecrosis and should be evaluated in larger patient cohorts.
AB - Osteonecrosis is a frequent complication after treatment for childhood leukemia and other steroid-based therapies. The success rate of core decompression surgery is limited. Therefore, we evaluated relevant biological characteristics of human multipotent mesenchymal stromal cells (MSCs) in vitro. MSCs cultured under low-oxygen tensions showed decreased proliferation and differentiation into bone. However, these MSCs secreted significant amounts of vascular endothelial-derived factor in the presence of interferon-gamma. These in vitro results with potential effects on neovascularization and bone regeneration as well as findings in animal models prompted us to treat five patients with steroid-induced osteonecrosis of the femur by core decompression surgery and instillation of expanded autologous MSCs. Within 3 weeks of culture, sufficient numbers of MSCs were generated using animal protein-free culture conditions. No chromosomal aberrations were detected by matrix-based comparative genomic hybridization. Application of MSCs during core decompression was feasible and safe. Median follow-up is 16 months and the patients in this pilot study reported clinical improvement. Formation of mineralized bone in the osteonecrotic cavity was proven by computed tomography. Taken together, MSCs display biological properties that may add to the efficiency of surgical treatment in osteonecrosis and should be evaluated in larger patient cohorts.
KW - Adolescent
KW - Adult
KW - Alkaline Phosphatase
KW - Bone Marrow Cells
KW - Bone Regeneration
KW - Cell Differentiation
KW - Cell Hypoxia
KW - Child
KW - Chromosomal Instability
KW - Comparative Genomic Hybridization
KW - Cytokines
KW - Enzyme-Linked Immunosorbent Assay
KW - Female
KW - Flow Cytometry
KW - Follow-Up Studies
KW - Humans
KW - Immunophenotyping
KW - Male
KW - Mesenchymal Stem Cell Transplantation
KW - Mesenchymal Stromal Cells
KW - Osteonecrosis
KW - Pilot Projects
KW - Radioimmunoassay
KW - Stromal Cells
KW - Tomography, X-Ray Computed
KW - Vascular Endothelial Growth Factor A
KW - Young Adult
U2 - 10.1038/leu.2008.217
DO - 10.1038/leu.2008.217
M3 - SCORING: Journal article
C2 - 18719618
VL - 22
SP - 2054
EP - 2061
JO - LEUKEMIA
JF - LEUKEMIA
SN - 0887-6924
IS - 11
ER -
