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Tissue Engineering and Regenerative Medicine International Society Asia Pacific Meeting 2011
In Vivo Maturation And Cell Integration Of Bioengineered Uterine Tissue
JK Williams , S Badra , J Yoo , A Atala
There are limited treatments for women with uterine factor infertility. Although uterine transplants have been proposed, they have been unsuccessful and require immunosuppression. An alternative approach is to bioengineer uterine tissue using autologous cells seeded on an absorbable matrix that integrates and repairs uterine defects of multiple sizes and shapes.
To investigate the feasibility of this approach, rabbit endometrial and myometrial cells were isolated from a uterine biopsy, labeled with lenti-GFP and then seeded on the interior or exterior surface (respectively) of co-polymer of polyglycolic acid with poly (lactide-co-glycolide) biodegradable scaffolds. Twenty-five rabbits received the autologous cell-seeded constructs for one partially removed uterine horn; whereas 6 rabbits received un-seeded constructs.
Over six months, the non-seeded constructs degraded to a non-structured, non-functional fibrotic mass. In contrast, the cell-seeded constructs formed neo-uterine tissue with distinct myometrial and endometrial layers and well defined secretory glands. Both native (GFP-), and seeded (GFP+) cells expressed tissue specific structural, functional, and integrative proteins in the myometrium, endometrium and secretory glands of the neo-uterine tissue. The neo-uterine tissue developed normal biomechanical properties and physiological response to pharmacologic stimuli which persisted for five years post-implantation. One of five rabbits receiving a cell-seeded construct conceived naturally and maintained the pregnancy to term, resulting in the birth of a live pup.
These data provide the feasibility of a tissue engineering approach for regeneration of large sections of uterine tissue and a model for a novel treatment of uterine related infertility.