Day 16, Lecture 1 (Sept. 14): Regenerative Medicine Flashcards Preview

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Flashcards in Day 16, Lecture 1 (Sept. 14): Regenerative Medicine Deck (22):

Tissue Regeneration

  • Occurs in a variety of human cells
    • e.g.
      • Skin
      • Liver
  • Many organs will not or poorly regenerate
    • e.g.
      • Neural Tissue
      • Kidney
  • Some organs will only regenerate partially depending on the defect
    • Scar formation
  • Often organ function can be impaired or lost after repair of large defects 
  • Tissue Regeneration
    • Restore injured, diseased or abnormal tissue
    • includes large variety of cell types
    • often requires local and systemic signals and factors


Tissue regeneration often requires ___ and _____ ____ and _____

Tissue regeneration often requires local and systemic signals and factors 


Tissue Engineering


The bladder contains ____, ___ and ____ cells

The bladder contains muscle, neural, and urothelial cells 


Can the bladder regenerate after injury



Example of congenital birth defect with Neurogenic bladders?

  • Neurogenic  bladder is a bladder that does not work
  • Congenital birth defects with neurogenic bladders 
    • Spina Bifida


Are there donor transplants for the bladder 

  • No
  • Difficult demands on transplant
    • Need to withstand toxic effects of urine
      • urine extravasation causes inflammation and fibrosis
    • Restoration fo bladder function 


What are the currently available options for bladder reconstruction

  • Intestinal segments
    • Bowel 
    • Stomach
  • Ureter


What are the problems associated with using intestinal segments for bladder transplant

  • Availability
  • Mucus formation
  • Stone formation
  • Hematuria
    • dysuria syndrome
  • Metabolic consequences


Why is there a need for engineered replacement tissues for the bladder

  • Avoid complications from intestinal segments
  • Save intestinal segments
  • Engineer tissue in vitro in desired quantities 


What is the difference between Unseeded Technique and Seeded Technique 

  • Unseeded Technique
    • Biodegradable scaffold
    • Transplanted into host
    • Native cells migrate into scaffold
    • Remodeled by the host into functional tissue
    • Depended on the organ's ability to regenerate itself 
  • Seeding of cultured cells onto biodegradle scaffold in vitro
  • Cell-Scaffold construct is transplanted into host
  • Construct is remodeled into functional tissue
  • Thought to 'jumpstart' the regeneration process




Cell lines suitable for bladder transplantation 

  • Differentiated cells cultured from bladder biopsies
  • Adult stem cells
  • Embryonic stem cells


Differentiated cells cultured from bladder biopsies 

  • Bladder biopsy taken form future transplant recipient
  • Primary culture of urothelial and smooth muscle cells in vitro
  • Transplantation of cultured cells into recipient 


Adult stem cells are derived from 


Embryonic stem cells are derived from


Porcine Small intestinal Submucosa in Bladder Regeneration

  • Plain Small intestinal submucosa (SIS) 
    • SIS acts as a scaffold for bladder augmentation
    • Problems:
      • Stone formation 
      • Graft contraction
    • Solution
      • Seed SIS prior to transplant
        • Less complications
        • Bigger Grafts 
  • SIS seeded with differentiated bladder cells
    • Cell-seeded SIS induces organized bladder regeneration in vivo
    • Problems:
      • Prior bladder biopsy necessary
      • Availability
        • congenital malformations
      • Pathologic cells
        • Congenital malformations
        • Malignant cells
    • Solution:
      • Alternative cell source
        • Adult stem cells
        • Embryonic stem cells 
  • SIS seeded with bone marrow derived stem cells
    • Expression of a-SM actin throughout whole graft 
    • SIS-BMSC contruct can regenerate the bladder
    • BMSC as alternative cell source in urologic tissue engineering
  • SIS seeded with human embryonic stem cells 
    • Pluripotent Human Stem Cells can be seeded on SIS for Tissue Engineering purposes
    • After implantation into the rat bladder they survive and can be detected for at least 28 days after surgery
    • Transplantation of Stem Cell seeded SIS demonstrates better acceptance of the graft into the host tissue and allows a superior regeneration of the injured bladder wall in comparison to non-seeded SIS 




What is the main problem in SIS bladder transplantation


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