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

Question 1

Tissue Regeneration

Answer 1

• 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

Question 2

Tissue regeneration often requires ___ and _____ ____ and _____

Answer 2

Tissue regeneration often requires local and systemic signals and factors

Question 3

Tissue Engineering

Answer 3

Question 4

The bladder contains ____, ___ and ____ cells

Answer 4

The bladder contains muscle, neural, and urothelial cells

Question 5

Can the bladder regenerate after injury

Answer 5

yes

Question 6

Example of congenital birth defect with Neurogenic bladders?

Answer 6

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

Question 7

Are there donor transplants for the bladder

Answer 7

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

Question 8

What are the currently available options for bladder reconstruction

Answer 8

• Intestinal segments
  
  • Bowel
  • Stomach
• Ureter

Question 9

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

Answer 9

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

Question 10

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

Answer 10

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

Question 11

What is the difference between Unseeded Technique and Seeded Technique

Answer 11

• 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

Question 12

Answer 12

Question 13

Question 14

Cell lines suitable for bladder transplantation

Answer 14

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

Question 15

Differentiated cells cultured from bladder biopsies

Answer 15

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

Question 16

Adult stem cells are derived from

Answer 16

Question 17

Embryonic stem cells are derived from

Answer 17

Question 18

Porcine Small intestinal Submucosa in Bladder Regeneration

Answer 18

• 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

Question 19

Answer 19

Question 20

Question 21

What is the main problem in SIS bladder transplantation

Answer 21

Question 22

Answer 22