Intestinal regeneration biology approach

Dr. Munira Shahbuddin

Tissue layers of gastrointestinal tract.

Intestinal development

Intestinal development from birth to adult

Intestinal development begins with the formation of the three germinal layers.

Various transcriptional factors associated with various region of the digestive tract

Hirshsprung disease

• Hirschsprung's disease (HD) is a disorder of the abdomen that occurs when part or all of the large intestine or antecedent parts of the gastrointestinal tract have no ganglion cells and therefore cannot function. During normal fetal development, cells from the neural crest migrate into the large intestine (colon) to form the networks of nerves called Auerbach's plexus and Meissner's plexus. In Hirschsprung's disease, the migration is not complete and part of the colon lacks these nerve bodies that regulate the activity of the colon.

Introduction to NSC transplantation

• The source of stem cells it the outmost important in the transplantation.

• NSC transplantation is driven by two significant findings:

1. Neuronal progenitor cells can be isolated from adult mammalian gut, including ganglionated colon of Hirschsprung’s patient

2. Progenitor cells can be induced to differentiate into several neuronal subtypes and glia characteristics.

Sources of smooth muscle and neuronal stem and progenitor cells

• In order to avoid immunosuppressive regiments, autologous stem cells sources are ideal.

• Bone marrow derived stem cells have been demonstrated to assume vascular and bladder smooth muscle phenotypes and have been widely used in regenerative medicine.

• Muscle derived stem cells can differentiate into myotubes as well as smooth muscle phenotypes.

• Within the postnatal gut, interstitial cells of Cajal have been shown to transdifferentiate into smooth muscle cells upon blockade of Kit signalling.

ENS as a source of Neural Crest Stem and Progenitor Cells

• The ENS is populated by migrating cells derived from the neural crest. Neural stem or progenitor cells have been isolated from embryonic, fetal, post natal and adult rodent guts.

• Enteric stem and progenitor cells have also been isolated from human full thickness/muscularis/mucosal gut biopsies.

• Neural progenitor stem cells also been isolated from ganglionated colons of Hirshsprung’s patients.

What are the differences between stem and progenitor cells?

Regenerating organogenesis

• Vertebrate intestinal regeneration in adults

• Mucosal development• Intestinal mucosal development takes place

broadly through two processes:• (1) morphogenesis, during which interactions

occur between the embryonic endoderm and the mesenchyme to form the tubular foregut, midgut, and hindgut, which then differentiate intocrypts and villi;

• (2) crypt differentiation of epithelial stem cells into four intestinal cell types (enterocytes, goblet cells, enteroendocrine cells, and Paneth cells).

Epimorphin expression in the colon. A Immunostaining for epimorphin expression in the colon. Two-colorimmunofluorescence was used to determine a-smooth muscle actin (SMA) expression (green) and epimorphin expression (red).Cells showing the coexpression of a-SMA and epimorphin are visualized by a yellow color

Inflammatory responses

Immunologic functions, which may be important in thepathogenesis of IBD, have not been fully investigatedin SEMFs. In many tissues, inflammatory responsesare regulated in close association with the regulationof ECM metabolism. For example, in colonic SEMFs,coupled induction of chemokines [IL-8 and monocytechemoattractant protein (MCP)-1] and MMPs in

responseto IL-1b and TNF-a has been observed

Fig. 5A–C. Bone marrow-derived SEMFs in the noninflamed(A, B) and inflamed (C) colonic mucosa. The Y chromosomeis detected as a brown dot in the cell nucleus (arrows). Redstaining of the cytoplasm reflects positivity for a-SMA.