2008
DOI: 10.1038/leu.2008.217
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Secretion of angiogenic proteins by human multipotent mesenchymal stromal cells and their clinical potential in the treatment of avascular osteonecrosis

Abstract: 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 interfer… Show more

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Cited by 64 publications
(49 citation statements)
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“…28,29 Of particular interest, very promising data from a pilot study on the clinical use of MSCs in the treatment of steroid-induced avascular osteonecrosis have recently reported in this journal. 30 Antiprotozoal and antiviral effector functions of MSCs, however, appear more relevant in the setting of allogeneic hematopoietic stem cell transplantation where severe infections with herpesviruses and intracellular parasites such as Toxoplasma gondii have a prominent role. 31 This is particularly noteworthy as MSCs are preferentially utilized in those patients suffering from GvHD who have failed several lines of pharmacological immunosuppressive therapy and therefore are severely immunodeficient.…”
Section: Discussionmentioning
confidence: 99%
“…28,29 Of particular interest, very promising data from a pilot study on the clinical use of MSCs in the treatment of steroid-induced avascular osteonecrosis have recently reported in this journal. 30 Antiprotozoal and antiviral effector functions of MSCs, however, appear more relevant in the setting of allogeneic hematopoietic stem cell transplantation where severe infections with herpesviruses and intracellular parasites such as Toxoplasma gondii have a prominent role. 31 This is particularly noteworthy as MSCs are preferentially utilized in those patients suffering from GvHD who have failed several lines of pharmacological immunosuppressive therapy and therefore are severely immunodeficient.…”
Section: Discussionmentioning
confidence: 99%
“…Thus, any additional factors decreasing MSC number or differentiation into osteoblasts may worsen the osteonecrotic process, induced by GC. This could explain why only a small fraction of patients receiving GC therapy develop ON and why a relatively small percentage of patients with positive radiograph and MRI osteonecrotic results are symptomatic (35). In the case of 6-MP therapy of the present study, decreased TPMT activity leads to greater bone marrow toxicity and decreased MSC number, which may impair bone formation and repair the forming osteonecrotic lesion.…”
mentioning
confidence: 79%
“…MSCs, cultured in the low-oxygen conditions, resembling those in the osteonecrotic lesion, were found to produce high levels of vasculogenic cytokines (35). Since vascular damage is speculated to be one of the primary ON causes, this induction of the vascularization by MSCs may lead to ON improvement (35). Thus, any additional factors decreasing MSC number or differentiation into osteoblasts may worsen the osteonecrotic process, induced by GC.…”
mentioning
confidence: 99%
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