regenerative medicine in urology latest .pptx

Regenerative medicine in urology latest guidelines

1. DR MAYANK YADAV MODERATOR – DR SOMENDRA BANSAL REGENERATIVE MEDICINE IN UROLOGY

2. William Haseltine , then the Scientific Founder and CEO of Human Genome Sciences, coined the term Regenerative medicine

3. Cells used Somatic cells Stem cells Limited proliferative ability ESC Induced pluripotent stem cells Somatic stem cells Perinatal stem cells/ fetal stem

4. Embryonic Stem Cells Totipotent cells Technique for the generation of embryonic stem cell lines Performing a single-cell embryo biopsy. Obtaining cells from arrested embryos Somatic cell nuclear transfer Ethical issue Teratoma Immunological rejection

5. Induced Pluripotent Stem Cells No ethical issue No immunological rejection

6. Adult Stem Cells/ somatic stem cell Multipotent Isolated from various tissues Hematopoeitic stem cell, MSC

7. Mesenchymal stem cell(MSC) Mc used immunomodulatory MSCs can be found in many tissues in large quantities Bone marrow mesenchymal stem cells Adipose derived mesenchymal cells

8. Perinatal Stem Cells Amniotic fluid and placental–derived stem (AFPS) cells Umbilical cord blood Multiple differentiating ability Less immunogenicity

9. Scaffolds What are they ? Importance

10. Synthetic matrices : PGA, PLGA advg Natural materials collagen, polysaccharides, fibrin, gelatin , cellulose Acellular matrices mc Preparation sources 3D bioprinting

11. Vascularization Limiting factor of engineered tissue Importance engineering large complex tissues, and possibly internal organs Three approaches Incorporation of angiogenic factors Seeding ECs Prevascularization

12. Soluble signals/ bioactive factors Soluble biomolecules Growth factors Cell adhesive molecules Chemokines Metalloprotein Importance cell viability cellular phenotype derive lineage specific differentiation

13. Tissue engineering in urology

14. TISSUE ENGINEERING OF URETHRA Congenital defects or post traumatic defects. Why do we need it ?

15. Urethra Naturally derived collagen based materials such as Woven meshes of PGA without cells and with cells Bladder derived acellular submucosa (BAM) Acellular urethral submucosa Collagen gels

16. Raya – Rivera et al 5 boys with urethral injuries Autolgous cells → seeded in two layers on tubularised PGA scaffoldings

17. Results Engineered urethras were able to show adequate anatomy, both by urethroscopy and by urethrography and function in long term

18. re

19. 6 patients (age 14 – 44 months) Cells harvested by cathetrisation and bladder lavage Lab cultured → seeded onto allogenic acellular dermis results → 3 pts developed complications (fistula and stricture) Conclusion - selected gp

20. Urinary bladder reconstruction Why we need it ? Regenerated bladder should Compliant muscular wall Well differentiated urothelium Acellular v/s cellular approach

21. Acellular approach Theory → scaffold recruits cells for new tissue formation Commonly used in studies BAM SIS Results →non seeded scaffolds fail to show full regeneration of the bladder wall Reason for failure→ early exposure of scaffold and newly implanted cells to urine, extensive scarring within graft,

22. Cellular approach

23. Acellular vs Cellular Oberpenning et al Canine model 3 groups Subtotal cystectomy subtotal cystectomy with non seeded scaffolds Subtotal cystectomy with seeded scaffold Results Cell seeded allogenic acellular bladder matrice showed better tissue regeneration.

24. First clinical trial of an engineered organ being implanted in human 9 pts of myelomeningocele Engineered human bladder tissue Autologous bladder biopsies Biodegradable 3 D matrix → collagen vs collagen and PGA f/u →46 months→ no metabolic complications/ stones/ mucus/ renal functions are preserved

25. Conclusion Composite scaffolds with omental wraps best results Important step in transfer of tissue engineering technology in clinical setting However, improvements in capacity not analogous to those achiwved by gold std.

26. Autologous seeded biodegradable scaffold ( tengion ) for bladder augmentation Outcomes Compliance Capacity Results 5 pt improved compliance Complications- all Conclusion

27. Replace ileal conduit with lab grown conduit Tengion’s neourinary conduit

28. Bladder Cell Therapies injectable therapy UI VUR Autologous smooth muscle cells Myoblasts Study Bladder exstrophy patients with UI 88% socially dry

29. Ureters challenges Scaffold Various animal studies Non seeded acellular grafts Cells seeded biodegradable polymer scaffolds Hybrid scaffolds 3D printing (poly 2 hydroxyethyl methylacrylate hydrogel )

30. Male Genital and Reproductive Tissues ED / Peyronie disease Conceptual Goals penile cell therapy ( muscle derived SC / adipose derived cells) Reconstruction of corporeal smooth muscle Engineered penile prosthesis .

31. Testis – leydig cells Patients with testicular dysfunction / anorchic ART Approaches Transplanting Leydig cells ( microencapsulated in an alginate- poly- L- Lysine solution ) Testicular prostheses advtg

32. Female Genital and Reproductive Tissues- uterus Cloacal exstrophy / intersex disorder Autologous rabbit uterine smooth muscle and epithelial cells Preconfigured uterine-shaped biodegradable polymer scaffolds

33. Vaginal reconstruction Engineered vaginal organs implanted into 4 pts with vaginal aplasia MRKHS Age 13-18 showed similar properties to those of normal vaginal tissue. Successful / no long term complications

34. Renal Structures Clinical problem ESRD One of the most difficult tissues to replicate in the laboratory. Application of regenerative medicine Cell therapy – clinical application still far away Bioengineering with ECM scaffolds .

35. Regenerative Medicine Approaches to Kidney Regeneration

36. Roadblocks

37. Future - Bioartificial kidney (BAK) Builds on concept of RAD Clinical trials on RAD The kidney project – goal Components

38. 3D bioprinting

39. Conclusion