Osteoinductivity of engineered cartilaginous templates devitalized by inducible apoptosis

被引:58
作者
Bourgine, Paul E. [1 ,2 ]
Scotti, Celeste [1 ,2 ,3 ]
Pigeot, Sebastien [1 ,2 ]
Tchang, Laurent A. [1 ,2 ]
Todorov, Atanas [1 ,2 ]
Martin, Ivan [1 ,2 ]
机构
[1] Univ Basel, Univ Basel Hosp, Dept Surg, CH-4031 Basel, Switzerland
[2] Univ Basel, Univ Basel Hosp, Dept Biomed, CH-4031 Basel, Switzerland
[3] IRCCS, Ist Ortoped Galeazzi, I-20161 Milan, Italy
基金
瑞士国家科学基金会;
关键词
developmental engineering; endochondral; osteoinductive; extracellular matrix; hematopoisesis; EXTRACELLULAR-MATRIX SCAFFOLDS; MESENCHYMAL STEM-CELLS; ANNEXIN-V; T-CELLS; IN-VIVO; BONE; DECELLULARIZATION; ORGAN; FUTURE; SAFETY;
D O I
10.1073/pnas.1411975111
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The role of cell-free extracellular matrix (ECM) in triggering tissue and organ regeneration has gained increased recognition, yet current approaches are predominantly based on the use of ECM from fully developed native tissues at nonhomologous sites. We describe a strategy to generate customized ECM, designed to activate endogenous regenerative programs by recapitulating tissue-specific developmental processes. The paradigm was exemplified in the context of the skeletal system by testing the osteoinductive capacity of engineered and devitalized hypertrophic cartilage, which is the primordial template for the development of most bones. ECM was engineered by inducing chondrogenesis of human mesenchymal stromal cells and devitalized by the implementation of a death-inducible genetic device, leading to cell apoptosis on activation and matrix protein preservation. The resulting hypertrophic cartilage ECM, tested in a stringent ectopic implantation model, efficiently remodeled to form de novo bone tissue of host origin, including mature vasculature and a hematopoietic compartment. Importantly, cartilage ECM could not generate frank bone tissue if devitalized by standard "freeze & thaw" (F&T) cycles, associated with a significant loss of glycosaminoglycans, mineral content, and ECM-bound cytokines critically involved in inflammatory, vascularization, and remodeling processes. These results support the utility of engineered ECM-based devices as off-the-shelf regenerative niches capable of recruiting and instructing resident cells toward the formation of a specific tissue.
引用
收藏
页码:17426 / 17431
页数:6
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