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A gut feeling about stem cell therapy for enteric neuropathies

Speaker
  • ARC DECRA Fellow, University of Melbourne
    Biography
      Dr. Lincon Stamp did his undergrad degree, BSc (Biotechnology) at the University of Newcastle (Australia). Here he developed a strong interest in stem cell biology and so moved to Melbourne to do Honours and then PhD with Prof Martin Pera at Monash University. Here his research involved investigation of the early differentiation of human embryonic stem cells toward hepatopancreatic cell fates. He then joined the lab of Dr. Don Newgreen at the Murdoch Children's Research Institute where he began working on development of the enteric nervous system, before joining Prof Heather Young's lab at the University of Melbourne Department of Anatomy and Neuroscience, where he has been focused on developing a stem cell therapy to treat gut motility disorders such as the pediatric enteric neuropathy Hirschprung disease. Lincon is an ARC DECRA Fellow and holds an NHMRC Project Grant as CIB with Prof Young, and has recently published a number of high impact studies in the Gastroenterology, Journal of Clinical Investigation and Stem Cell Reports.

    Abstract

    The enteric nervous system (ENS) plays an essential role in gut motility. Diseases of the ENS result in bowel motility disorders that are some of the most challenging clinical conditions to manage. Cell therapy offers the potential to treat gastrointestinal motility disorders caused by enteric neuropathies. We have previously shown that following transplantation into the colon of recipient mice, enteric neural progenitors proliferate, migrate and differentiate into a variety of neurochemical types of neurons. However, it was unclear whether graft-derived neurons integrate into the circuitry of the recipient and directly regulate gut motility. We have used optogenetic and electrophysiological approaches to examine whether transplanted enteric neural progenitors generate neurons that functionally innervate the colon. Neural progenitors expressing the light-sensitive ion channel, channelrhodopsin, were isolated from fetal or postnatal bowel and transplanted into the colon of postnatal mice. The responses of recipient colonic smooth muscle cells to light stimulation of graft-derived neurons were examined. Light stimulation of graft-derived cells resulted in excitatory and inhibitory junction potentials, the electrical events underlying contraction and relaxation respectively, in colonic circular muscle cells. The pharmacological properties of the junction potentials evoked by stimulation of graft-derived neurons were identical to those of endogenous excitatory and inhibitory motor neurons. Interneurons were also generated from graft-derived cells, but their pharmacological properties varied with the age of the donors from which the progenitors were obtained. Our data demonstrate that transplanted progenitors generate different functional classes of enteric neurons involved in the control of gut motility.


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