Campbell-Walsh Urology, 11th Edition

PART IV

Molecular and Cellular Biology

20

Principles of Tissue Engineering

Anthony Atala

Questions

  1. Currently, possible tissue replacements for reconstruction include which of the following?
  2. Native nonurologic tissues
  3. Homologous tissues
  4. Heterologous tissues
  5. Artificial biomaterials
  6. All of the above
  7. What does tissue engineering involve?
  8. The principles of cell transplantation
  9. The principles of materials science
  10. The use of matrices alone
  11. The use of matrices with cells
  12. All of the above
  13. In regenerative medicine, when autologous cells are used:
  14. donor tissue is dissociated into individual cells.
  15. cells are either implanted directly into the host or expanded in culture.
  16. cells are attached to a support matrix.
  17. the cells and matrix are implanted in vivo.
  18. all of the above.
  19. Which of the following statements is TRUE regarding biomaterials?
  20. They facilitate the localization and delivery of cells.
  21. They facilitate the localization and delivery of bioactive factors.
  22. They define a three-dimensional space for the formation of new tissues.
  23. They guide the development of new tissues with appropriate function.
  24. All of the above.
  25. Types of biomaterials that have been utilized for engineering genitourinary tissues include which of the following?
  26. Naturally derived materials
  27. Acellular tissue matrices
  28. Synthetic polymers
  29. All of the above
  30. None of the above
  31. Procedures and techniques that allow for the exclusion of nonurologic tissues during augmentation cystoplasty include which of the following?
  32. Autoaugmentation
  33. Ureterocystoplasty
  34. Tissue expansion
  35. Tissue engineering
  36. All of the above
  37. Permanent synthetic materials, when used in continuity with the urinary tract, have been associated with:
  38. mechanical failure.
  39. emboli.
  40. calculus formation.
  41. a and c.
  42. none of the above.
  43. Urothelium is associated with:
  44. a high reparative capacity.
  45. an inherent capacity for artificial extracellular matrix attachment.
  46. frequent malignant differentiation.
  47. poor growth parameters.
  48. none of the above.
  49. Major limitations in phallic reconstructive surgery include which of the following?
  50. The availability of adequate growth factors
  51. The availability of sufficient autologous tissue
  52. The availability of adequate surgical techniques
  53. All of the above
  54. None of the above
  55. What is the most prevalent form of renal replacement therapy?
  56. Organ transplantation
  57. Dialysis
  58. Bioartificial hemofilters
  59. Bioartificial renal tubules
  60. Engineered functional renal structures
  61. The ideal bulking substance for the endoscopic treatment of reflux and incontinence should have what characteristic(s)?
  62. Easily injectable
  63. Nonantigenic
  64. Nonmigratory
  65. Volume stable
  66. All of the above
  67. What are the most common cell sources for regenerative medicine today?
  68. Embryonic stem cells
  69. Induced pluripotent stem cells
  70. Autologous cells
  71. Stem cells derived from nuclear transfer techniques
  72. None of the above

Answers

  1. e. All of the above.Whenever there is a lack of native urologic tissue, reconstruction may be performed with native nonurologic tissues (skin, gastrointestinal segments, or mucosa from multiple body sites), homologous tissues (cadaver fascia, cadaver or donor kidney), heterologous tissues (bovine collagen), or artificial materials (silicone, polyurethane, Teflon [DuPont, Wilmington, DE]).
  2. e. All of the above.Regenerative medicine follows the principles of cell transplantation, materials science, and engineering toward the development of biologic substitutes that would restore and maintain normal function. Tissue engineering may involve matrices alone, wherein the body's natural ability to regenerate is used to orient or direct new tissue growth, or the use of matrices with cells.
  3. e. All of the above.When cells are used for regenerative medicine, donor tissue is dissociated into individual cells, which either are implanted directly into the host or are expanded in culture, attached to a support matrix, and reimplanted after expansion. The implanted tissue can be heterologous, allogeneic, or autologous.
  4. e. All of the above.Biomaterials are used to facilitate the localization and delivery of cells and/or bioactive factors (e.g., cell adhesion peptides and growth factors) to desired sites in the body, define a three-dimensional space for the formation of new tissues with appropriate structure, and guide the development of new tissues with appropriate function.
  5. d. All of the above.Generally, three classes of biomaterials have been used for engineering genitourinary tissues: naturally derived materials (e.g., collagen and alginate), acellular tissue matrices (e.g., bladder submucosa and small intestinal submucosa), and synthetic polymers (e.g., polyglycolic acid [PGA], polylactic acid [PLA], and poly(lactic-co-glycolic acid) [PLGA]).
  6. e. All of the above.Because of the problems encountered with the use of gastrointestinal segments, numerous investigators have attempted alternative methods, materials, and tissues for bladder replacement or repair. These include autoaugmentation, ureterocystoplasty, methods for tissue expansion, seromuscular grafts, matrices for tissue regeneration, and tissue engineering using cell transplantation.
  7. d. a and c.Usually, permanent synthetic materials used for bladder reconstruction succumb to mechanical failure and urinary stone formation, and degradable materials lead to fibroblast deposition, scarring, graft contracture, and a reduced reservoir volume over time.
  8. a. a high reparative capacity.It has been well established for decades that the bladder is able to regenerate generously over free grafts. Urothelium is associated with a high reparative capacity. Bladder muscle tissue is less likely to regenerate in a normal manner.
  9. b. The availability of sufficient autologous tissue.One of the major limitations of phallic reconstructive surgery is the availability of sufficient autologous tissue.
  10. b. Dialysis.Although dialysis therapy is currently the most prevalent form of renal replacement therapy, the relatively high morbidity and mortality rates have prompted investigators to seek alternative solutions involving ex vivo systems.
  11. e. All of the above.The ideal substance for the endoscopic treatment of reflux and incontinence should be injectable, nonantigenic, nonmigratory, volume stable, and safe for human use.
  12. c. Autologous cells.Most current strategies for engineering urologic tissues involve harvesting of autologous cells from the host diseased organ or from donor cells from other sources from the patient, such as fat or bone marrow. However, in situations in which extensive end-stage organ failure is present, a tissue biopsy may not yield enough normal cells for expansion. Under these circumstances, the availability of pluripotent stem cells may be beneficial.

Chapter review

  1. Stem cells may be either embryonic or adult. Embryonic stem cells may be harvested from (1) a blastocyst, (2) amniotic fluid, or (3) the placenta. Adult stem cells are usually isolated from a specific organ or bone marrow.
  2. Stem cells have the ability to self-renew, to differentiate into a number of cell types, and to form clonal populations.
  3. Altered nuclear transfer is a technique in which a genetically modified nucleus from a somatic cell is transferred into a human oocyte. The resulting embryo develops into a blastocyst but cannot implant into a uterus. The ethical advantage is that a fully developed organism is not created.
  4. Adult stem cells have been discovered in many organs in the body and may serve as primary mechanisms of repair for injuries of these organs.
  5. The ideal biomaterial provides regulation of cell behavior to promote development of functional new tissue. The cell behavior regulated includes but is not limited to cell adhesion, proliferation, migration, and differentiation. There are three types of biomaterials that are used: (1) naturally derived materials such as collagen or alginate (a polysaccharide isolated from seaweed), (2) acellular tissue matrices such as bladder submucosa or small intestine submucosa, and (3) synthetic polymers such as polyglycolic acid.
  6. Formation of new blood vessels and capillaries occur by two mechanisms: vasculogenesis, in which new capillaries are formed from undifferentiated cells, and angiogenesis, in which new capillaries form by sprouting from preexisting capillaries.
  7. In normal wound healing, epithelial cell ingrowth is initiated from the wound edges. This type of healing results in normal epithelium for no more than a distance of a few millimeters. Beyond that limit, fibrosis and scar formation occur in the rest of the wound. Matrices or matrices implanted with cells on the open wound allow greater wound coverage with the hope of less fibrosis. Cell-seeded matrices are superior to nonseeded matrices.
  8. Most free grafts for bladder replacement show an adequate urothelial layer, but the muscular layer is not fully developed. SIS (small intestine submucosa), a biodegradable, acellular, xenogeneic collagen based tissue matrix graft, has been successfully employed in surgical correction of urethral strictures and Peyronie disease.