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Tissue engineering applications in urology
- 1. Tissue engineering Applications in Urology Dr. Roshan V Shetty Senior Resident In Urology AJIMS &RC
- 2. Organ transplantation Tissue for reconstructive procedures Novel therapies for chronic illness
- 3. Normal wound healing has been studied extensively and is helpful in maximizing success for the engineering of tissues At the time of tissue injury, cell ingrowth is initiated from the wound edges to cover the tissue defect Cells are able to traverse short distances without any detrimental effects wound is large, more than a few millimeters in distance or depth, increased collagen deposition, fibrosis, and scar formation ensue
- 4. Matrices implanted in wound beds are able to lengthen the distances that cells can traverse Tissue defects greater than 1 cm that are treated with a matrix alone, without cells, usually have increased collagen deposition Cell-seeded matrices implanted in wound beds are able to further lengthen the distance for normal tissue formation without initiating an adverse fibrotic response
- 5. Urethra Naturally derived collagen-based materials such as Woven meshes of PGA without cells and with cells bladder-derived acellular submucosa acellular urethral submucosa collagen gels bladder submucosa matrix proved to be a suitable graft for repair of urethral defects Nonseeded acellular matrices, were applied in a successful manner for onlay urethral repairs
- 6. Urethra Atala et al, 1999 Neourethras were created by anastomosing the matrix in an on- lay fashion to the urethral plate size of the created neourethra ranged from 5 to 15 cm After a 3-year follow-up, 3 or 4 patients had a successful outcome with regard to cosmetic appearance and function One patient who had a 15-cm neourethra created developed a sub-glanular fistula
- 7. Urethra Acellular collagen-based matrix Eliminated the necessity of additional surgical procedures for graft harvesting, Potential morbidity from the harvest procedure were decreased Reduced operative time But when tubularized urethral repairs were attempted experimentally, adequate urethral tissue regeneration was not achieved and complications ensued(contracture & Stricture).
- 8. Urethra To overcome this bladder epithelial and smooth muscle cells were grown and seeded onto preconfigured tubular matrices Entire urethra segments were resected and urethroplasties were performed with tubularized collagen matrices seeded with cells
- 9. Urethra Raya-Rivera et al, 2011 5 patients with urethral injuries had a small tissue biopsy specimen retrieved cells were expanded in vitro and seeded in two layers on tubularized scaffolds that were implanted surgically engineered urethras were able to show adequate anatomy, both by urethroscopy and with urethrography and function long term
- 11. Bladder Currently, gastrointestinal segments are commonly used as tissues for bladder replacement or repair GI tissues are designed to absorb specific solutes whereas bladder tissue is designed for the excretion of solutes Thus, multiple complications may ensue, such as infection, metabolic disturbances, urolithiasis, perforation, increased mucus production, and malignancy
- 12. Bladder Matrices Synthetic materials that have been tried include polyvinyl sponge, Teflon, collagen matrices, Vicryl (PGA) matrices, and silicone Permanent synthetic materials used for bladder reconstruction succumb to mechanical failure and urinary stone formation use of degradable materials leads to fibroblast deposition, scarring, graft contracture, and a reduced reservoir volume over time
- 13. Bladder Non-seeded allogeneic acellular bladder matrices have served as scaffolds for the ingrowth of host bladder wall components serve as vehicles for partial bladder regeneration Acellular collagen matrices can be enhanced with growth factors to improve bladder regeneration Cell-seeded allogeneic acellular bladder matrices showed better tissue regeneration
- 14. Bladder SIS, a biodegradable, acellular, xenogeneic collagen-based tissue matrix graft, was first described in early 1960s derived from pig small intestine in which mucosa is mechanically removed from inner surface and serosa and muscular layer are removed from outer surface Non seeded SIS matrix used for bladder augmentation is able to regenerate in vivo transitional layer was the same as that of the native bladder tissue but muscle layer was not fully developed
- 15. Bladder Regenerative medicine with selective cell transplantation in SIS may provide a means to create functional new bladder segments. Native cells are currently preferable because they can be used without rejection Amniotic fluid– and bone marrow–derived stem cells have the potential to differentiate into bladder tissue and urothelium. Embryonic stem cells also have the potential to differentiate into bladder tissue.
- 16. Bladder A study using engineered bladder tissue for cystoplasty reconstruction was conducted starting in 1998 pilot study of seven patients was reported , Atala et al, 2006 Patients underwent reconstruction with the engineered bladder tissue created with the PGA-collagen cell-seeded scaffolds with omental coverage showed increased compliance, decreased end-filling pressures, increased capacities, and longer dry periods over time
- 17. Bladder
- 18. Bladder cell therapies Injectable therapy within the bladder may be useful for SUI and VUR Injection of chondrocytes for the correction of VUR in children At 1-year follow-up, reflux correction was maintained in 70% SUI in adults have been attempted After 1 year, 1/8 women achieved total continence and 5 reported improvement
- 19. Bladder cell therapies autologous smooth muscle cells was explored for urinary incontinence, SUI and VUR applications myoblasts isolated from the abdominal wall vasculature were injected in a series of bladder exstrophy patients with urinary incontinence. 88% of patients were socially dry The patients were also on a pelvic floor electrical stimulation and pelvic floor exercise program
- 20. Ureters Collagen tubular sponges Ureteral decellularized matrices Cell-seeded biodegradable polymer scaffolds have been used as cell transplantation vehicles to reconstruct ureteral tissues Urothelial and smooth muscle cells isolated from bladders and expanded in vitro were seeded onto PGA scaffolds with tubular configurations and implanted subcutaneously resulted in the eventual formation of natural urothelial tissues
- 21. Male Genital And Reproductive Tissue One of the major limitations of genital reconstructive surgery is the availability of sufficient autologous tissue Phallic reconstruction was initially attempted in the late 1930s, with rib cartilage but discouraged because of the unsatisfactory functional and cosmetic results Silicone rigid prostheses were popularized in the 1970s and have been used widely but biocompatibility issues have been a problem
- 22. Male Genital And Reproductive Tissue Reconstruction of Penile Corpora Cultured human corporeal smooth muscle cells may be used in conjunction with biodegradable polymers to create corpus cavernosum tissue de novo Falke et al, 2003 Human corpus cavernosal muscle and ECs were derived from donor penile tissue, and the cells were expanded in vitro and seeded on the acellular matrices. The matrices were covered with the appropriate cell architecture 4 weeks after implantation
- 23. Male Genital And Reproductive Tissue Reconstruction of Penile Corpora Experimental corporeal bodies demonstrated intact structural integrity by cavernosography and showed similar pressure by cavernosometry when compared with normal controls Mating activity in the animals with the engineered corpora appeared normal by 1 month after implantation Sperm was present in all and were able to father healthy offspring.
- 24. Male Genital And Reproductive Tissue Penile Cell Therapy Various cell lines have been used in animal models in an attempt to reverse erectile dysfunction in animal models Endothelial cells Mesenchymal stem cells either alone or with matrices human bone marrow–derived stem cells Muscle-derived stem cells Long-term studies are needed to gauge the full impact of these therapies
- 25. Penile transplant Such a scaffold could represent a new solution in cases of total penile loss after cancer or trauma or in transgender surgeries, cases where the incidence is increasing rapidly.
- 26. Male Genital And Reproductive Tissue Testis – Leydig cells Patients with testicular dysfunction require androgen replacement for somatic development in form of periodic intramuscular injections Skin patch applications Long-term non-pulsatile testosterone therapy is not optimal and can cause multiple problems
- 27. Male Genital And Reproductive Tissue Testis – Leydig cells Leydig cells were microencapsulated in an alginate-poly-L- lysine solution for controlled testosterone replacement Provides a barrier between the transplanted cells and the host’s immune system, as well as allowing for the long-term physiologic release of testosterone On similar principles, testicular prostheses have been created with chondrocytes and loaded with testosterone
- 28. Male Genital And Reproductive Tissue Testis – Spermatogenesis Spermatogenesis for infertility purposes has been a major area of interest First successful isolation of human spermatogonial stem cells in 2002 showed that the cells were able to colonize and survive for 6 months in mice recipient testes Successful autologous and allogeneic spermatogonial stem cell transplantation has been demonstrated In vitro propagation of human spermatogonial stem cells from both adult and pubertal testes has been established
- 29. Female Genital And Reproductive Tissue Uterus Congenital malformations of the uterus may have profound implications clinically possibility of engineering functional uterine tissue using autologous cells was investigated Autologous uterine smooth muscle and epithelial cells were harvested, grown, and expanded in culture. These cells were seeded onto preconfigured uterine-shaped biodegradable polymer scaffolds, which were then used for subtotal uterine tissue replacement
- 30. Female Genital And Reproductive Tissue Vagina Many techniques and materials can be used successfully for vaginal reconstruction most common, creating a canal by dissecting the potential neovaginal space and subsequently lining the pelvic canal with a graft Vaginal epithelial and smooth muscle cells were harvested, expanded, and seeded on biodegradable polymer scaffolds
- 32. Female Genital And Reproductive Tissue Ovary Ovarian tissue is essential for fertility. Recent studies have shown that ovarian cells can be derived from stem cell populations. The cells can lead to the production of oocytes and embryos Cell therapies have also been used to enhance the functionality of the ovary Adipose-, amniotic fluid–, umbilical cord–, and bone marrow–derived stem cells have all resulted in a return of experimentally damaged ovarian function in animal models
- 33. Renal Structures Isolation of particular cell types that produce specific factors may be a good approach for selective cell therapies Cells that produce erythropoietin have been isolated in culture, and these cells could eventually be used to treat anemia that results from ESRD More ambitious approaches involve working toward the goal of total renal function replacement
- 34. Renal Structures Nuclear material from bovine dermal fibroblasts was transferred into unfertilized enucleated eggs. Renal cells from the cloned embryos were harvested, expanded in vitro, and seeded onto three-dimensional renal devices. The devices were implanted into the back into the steer and were retrieved 12 weeks later. This process produced functioning renal units Cells derived from nuclear transfer can be successfully harvested, expanded in culture, and transplanted in vivo with the use of biodegradable scaffolds on which the single suspended cells can organize into tissue
- 36. Renal Structures These studies were the first demonstration of the use of therapeutic cloning for regeneration of tissues in vivo Renal cells seeded on the matrix adhered to the inner surface and proliferated to confluency by 7 days after seeding. Renal tubular and glomerulus-like structures were observed 8 weeks after implantation More recent data has confirmed that the creation of larger kidney structures using decellularized kidney matrices and repopulated with cells is possible
- 37. Thank You