Bioengineered internal anal sphincter constructs and methods of use thereof
AssigneeCellf-Bio, Inc.
InventorsKhalil Nakhle Bitar, Prabhash Dadhich
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Abstract
Disclosed herein are internal anal sphincter constructs, and methods for generating and/or using such constructs. Also provided herein are methods for using internal anal sphincter construct(s) for treating fecal incontinence in a subject. The method of generating an innervated internal anal sphincter construct, provided herein, comprises using smooth muscle cells (SMCs) from an anorectum tissue cell biopsy and neural progenitor cells (NPCs) from an intestinal tissue cell biopsy from the subject.
Claims38
A method of generating an innervated internal anal sphincter construct, comprising:
- isolating smooth muscle cells (SMCs) from an anorectum tissue cell biopsy from a subject;
- isolating neural progenitor cells (NPCs) from an intestinal tissue cell biopsy from the subject;
- suspending the NPCs in collagen and/or laminin hydrogel, and mixing the NPCs with the SMCs to provide a cell mix;
- seeding the cell mix as a single-layer hydrogel matrix on a mold and allowing gelation of the cell mix around a central post;
- contacting the single-layer hydrogel matrix with a neural differentiation media;
- and
- allowing maturation of the single-layer hydrogel matrix and differentiation of the NPCs, thereby forming the innervated internal anal sphincter construct having directionally oriented SMCs.
A method for treating fecal incontinence (FI) in a subject in need thereof, the method comprising:
- isolating smooth muscle cells (SMCs) from an anorectum tissue cell biopsy obtained from the subject;
- isolating neural progenitor cells (NPCs) from an intestinal tissue cell biopsy obtained from the subject;
- suspending the NPCs in collagen and/or laminin hydrogel, and mixing the NPCs with the SMCs to provide a cell mix;
- seeding the cell mix as a single-layer hydrogel matrix on a mold and allowing gelation of the cell mix around a central post;
- contacting the single-layer hydrogel matrix with a neural differentiation media;
- allowing maturation of the single-layer hydrogel matrix and differentiation of the NPCs, thereby forming an innervated internal anal sphincter construct having directionally oriented SMCs;
- and
- implanting the innervated internal anal sphincter construct to the subject, wherein the implantation is through a circumferential dissection around the anorectum of the subject.
Dependencies are inferred from the claim text.