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Human-scale lung regeneration based on decellularized matrix scaffolds as a biologic platform
Keiji Ohata1,2, Harald C Ott3,4
1Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, CPZN 4800, Boston, MA, 02114, USA.
Surgery Today
|May 5, 2020
Summary
Creating bioartificial lungs from decellularized scaffolds and patient-derived cells shows promise for treating lung disease. This approach aims to overcome donor organ shortages and reduce immunosuppression needs for future lung transplants.
Area of Science:
- Regenerative Medicine
- Biomaterials Science
- Transplantation Biology
Background:
- Lung transplantation is the only cure for end-stage lung disease but faces donor organ scarcity and immunosuppression challenges.
- Bioartificial lungs, using decellularized native lung scaffolds and patient cells, offer a potential solution.
- Decellularization removes cells, preserving the extracellular matrix scaffold for recellularization.
Purpose of the Study:
- To investigate the feasibility of creating transplantable bioartificial lungs using decellularized lung scaffolds.
- To evaluate the potential of patient-derived cells, including induced pluripotent stem cells (iPSCs), for recellularizing lung scaffolds.
- To assess the early functional outcomes of bioartificial lung transplantation in preclinical models.
Main Methods:
- Detergent perfusion to decellularize cadaveric lungs, preserving extracellular matrix architecture.
- Recellularization of lung scaffolds in a bioreactor with biomimetic conditions (vascular perfusion, liquid ventilation).
- Whole-organ culture for cell seeding, engraftment, and tissue maturation.
- Transplantation of bioartificial lungs in rat and porcine models.
Main Results:
- Decellularized lung scaffolds retained native vascular and airway architecture.
- Successful vascular and airway anastomoses were achieved in transplantation models.
- Evidence of gas exchange was observed after reperfusion in transplanted bioartificial lungs.
- Long-term function was limited by immature vascular beds and distal lung epithelia.
Conclusions:
- Bioartificial lungs are transplantable, preserving essential anatomical structures.
- Current limitations include the immaturity of regenerated lung tissues, hindering long-term function.
- Patient-specific bioartificial lungs using iPSC-derived cells represent a promising future direction for regenerative medicine in lung transplantation.
