Heterotopic ossification(HO)is a debilitating condition characterized by the pathologic formation of ectopic bone.HO occurs commonly following orthopedic surgeries,burns,and neurologic injuries.While surgical excision...Heterotopic ossification(HO)is a debilitating condition characterized by the pathologic formation of ectopic bone.HO occurs commonly following orthopedic surgeries,burns,and neurologic injuries.While surgical excision may provide palliation,the procedure is often burdened with significant intra-operative blood loss due to a more robust contribution of blood supply to the pathologic bone than to native bone.Based on these clinical observations,we set out to examine the role of vascular signaling in HO.Vascular endothelial growth factor A(VEGFA)has previously been shown to be a crucial pro-angiogenic and pro-osteogenic cue during normal bone development and homeostasis.Our findings,using a validated mouse model of HO,demonstrate that HO lesions are highly vascular,and that VEGFA is critical to ectopic bone formation,despite lacking a contribution of endothelial cells within the developing anlagen.展开更多
Mesenchymal stem cells(MSCs)have long been regarded as critical components of regenerative medicine strategies,given their multipotency and persistence in a variety of tissues.Recently,the specific role of MSCs in med...Mesenchymal stem cells(MSCs)have long been regarded as critical components of regenerative medicine strategies,given their multipotency and persistence in a variety of tissues.Recently,the specific role of MSCs in mediating regenerative outcomes has been attributed(in part)to secreted factors from transplanted cells,namely extracellular vesicles.This viewpoint manuscript highlights the promise of cell-derived extracellular vesicles as agents of regeneration,enhanced by synergy with appropriate biomaterials platforms.Extracellular vesicles are a potentially interesting regenerative tool to enhance the synergy between MSCs and biomaterials.As a result,we believe these technologies will improve patient outcomes through efficient therapeutic strategies resulting in predictable patient outcomes.展开更多
基金B.L.:Supported by funding from NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH1R01AR071379American College of Surgeons Clowes Award.D.M.S.:Supported by Plastic Surgery Foundation Resident Research Award+6 种基金M.S.:Supported by Plastic Surgery Foundation National Endowment AwardC.H.:Supported by Howard Hughes Medical Institute Medical Research FellowshipJ.L.:Supported by Vascular Surgery T32 5-T32-HL-076123–14A.W.J.:Supported by the NIH/NIAMS(R01 AR070773,K08 AR068316,S10OD016374)the Orthopedic Research and Education Foundation with funding provided by the Maryland Stem Cell Research Foundation,and the Musculoskeletal Transplant FoundationP.B.Y.:Supported by funding from NIH/NIAMS R01 AR057374 and NHLBI R01 HL131910Y.M.:Supported by funding from NIH/NIDCR R01 DE020843 and DE027662
文摘Heterotopic ossification(HO)is a debilitating condition characterized by the pathologic formation of ectopic bone.HO occurs commonly following orthopedic surgeries,burns,and neurologic injuries.While surgical excision may provide palliation,the procedure is often burdened with significant intra-operative blood loss due to a more robust contribution of blood supply to the pathologic bone than to native bone.Based on these clinical observations,we set out to examine the role of vascular signaling in HO.Vascular endothelial growth factor A(VEGFA)has previously been shown to be a crucial pro-angiogenic and pro-osteogenic cue during normal bone development and homeostasis.Our findings,using a validated mouse model of HO,demonstrate that HO lesions are highly vascular,and that VEGFA is critical to ectopic bone formation,despite lacking a contribution of endothelial cells within the developing anlagen.
基金This work was supported by the National Institutes of Health(NIH):R01-DE027662(YM),F30-DE029359(WBS).
文摘Mesenchymal stem cells(MSCs)have long been regarded as critical components of regenerative medicine strategies,given their multipotency and persistence in a variety of tissues.Recently,the specific role of MSCs in mediating regenerative outcomes has been attributed(in part)to secreted factors from transplanted cells,namely extracellular vesicles.This viewpoint manuscript highlights the promise of cell-derived extracellular vesicles as agents of regeneration,enhanced by synergy with appropriate biomaterials platforms.Extracellular vesicles are a potentially interesting regenerative tool to enhance the synergy between MSCs and biomaterials.As a result,we believe these technologies will improve patient outcomes through efficient therapeutic strategies resulting in predictable patient outcomes.
