Tissue decellularization by activation of programmed cell death

Bourgine, Paul; Pippenger, Benjamin E.; Todorov, Atanas; Tchang, Laurent A.; Martin, Ivan

doi:10.1016/j.biomaterials.2013.04.058

Cited by 70 publications

(77 citation statements)

References 77 publications

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“…Decellularization of tissue engineered grafts represents a promising strategy to accelerate the translation of such therapies into the clinic by providing 'off-the-shelf' constructs that can facilitate endogenous tissue or organ regeneration [34][35][36]. The results of this study provide support for the hypothesis that a porous scaffold generated from hypertrophic cartilage ECM, engineered using allogeneic MSCs, will support vascularization and host-mediated bone formation upon implantation.…”

Section: Discussionsupporting

confidence: 52%

Porous decellularized tissue engineered hypertrophic cartilage as a scaffold for large bone defect healing

et al. 2015

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Clinical translation of tissue engineered therapeutics is hampered by the significant logistical and regulatory challenges associated with such products, prompting increased interest in the use of decellularized extracellular matrix (ECM) to enhance endogenous regeneration. Most bones develop and heal by endochondral ossification, the replacement of a hypertrophic cartilaginous intermediary with bone. The hypothesis of this study is that a porous scaffold derived from decellularized tissue engineered hypertrophic cartilage will retain the necessary signals to instruct host cells to accelerate endogenous bone regeneration. Cartilage tissue (CT) and hypertrophic cartilage tissue (HT) were engineered using human bone marrow derived mesenchymal stem cells, decellularized and the remaining ECM was freeze-dried to generate porous scaffolds. When implanted subcutaneously in nude mice, only the decellularized HT-derived scaffolds were found to induce vascularization and de novo mineral accumulation. Furthermore, when implanted into critically-sized femoral defects, full bridging was observed in half of the defects treated with HT scaffolds, while no evidence of such bridging was found in empty controls. Host cells which had migrated throughout the scaffold were capable of producing new bone tissue, in contrast to fibrous tissue formation within empty controls. These results demonstrate the capacity of decellularized engineered tissues as 'off-the-shelf' implants to promote tissue regeneration.

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Section: Discussionsupporting

confidence: 52%

Porous decellularized tissue engineered hypertrophic cartilage as a scaffold for large bone defect healing

et al. 2015

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“…The multitude of parameters involved may also require the use of miniaturized high-throughput devices (e.g. microfluidic devices) followed by combinatorial analyses in order to define the minimal set of necessary eECM signals which are required for predictable instruction of bone regeneration [84].…”

Section: Discussionmentioning

confidence: 99%

“…Existing strategies rely on physical, chemical or enzymatic treatment that fail to achieve an efficient cell removal while preserving the bioactive ECM elements. A valuable direction may be represented by the specific activation of the apoptotic cell program [84], to selectively target the killing of the cellular fraction while reducing the side effects of ECM damage.…”

Section: Standardization Of Eecmmentioning

confidence: 99%

Engineered decellularized matrices to instruct bone regeneration processes

Papadimitropoulos

Scotti

Bourgine

et al. 2015

Bone

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“…S2), which was previously proposed to target the living cell fraction with minimal changes in the ECM components (18). Primary hMSCs were thus retrovirally transduced with a death system based on the inducible dimerization of modified caspase 9 (iDS; Fig.…”

Section: Generation Of Hypertrophic Constructs Using Death-inducible mentioning

confidence: 99%

“…This implies the use of a devitalization strategy reducing alterations in the composition and architecture of the generated template to mimic both the physiologic regenerative milieu and the 3D structure of the fracture callus. Toward this objective, a devitalization approach has been proposed via the induction of apoptosis (18). In particular, an inducible genetic system (19) can be incorporated into primary hMSCs to specifically induce their apoptosis on exposure to a clinical-grade chemical compound.…”

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confidence: 99%

Osteoinductivity of engineered cartilaginous templates devitalized by inducible apoptosis

Bourgine

Scotti

Pigeot

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance It has been previously reported that hypertrophic cartilage tissues engineered from human mesenchymal stromal cells can efficiently remodel in vivo into bone organs, recapitulating developmental steps of endochondral ossification. We have here demonstrated that the extracellular matrix (ECM) of such engineered cartilage, even in the absence of a living cell component, retains frankly osteoinductive properties. The use of an apoptosis-driven devitalization technique revealed the importance of preserving the ECM integrity and, in particular, the embedded factors to trigger the regenerative process. Although exemplified in a skeletal context, our work outlines the general paradigm of cell-based but cell-free off-the-shelf materials capable of activating endogenous cells toward the formation of specific tissues.

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Tissue decellularization by activation of programmed cell death

Cited by 70 publications

References 77 publications

Porous decellularized tissue engineered hypertrophic cartilage as a scaffold for large bone defect healing

Porous decellularized tissue engineered hypertrophic cartilage as a scaffold for large bone defect healing

Engineered decellularized matrices to instruct bone regeneration processes

Osteoinductivity of engineered cartilaginous templates devitalized by inducible apoptosis

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