Method of organogenesis and tissue regeneration/repair using surgical techniques

• US 6,227,202 B1
• Filed: 08/29/1997
• Issued: 05/08/2001
• Est. Priority Date: 09/03/1996
• Status: Expired due to Fees

• Current Assignee: National Research Development Corporation
• Original Assignee: Maulana Azad Medical College (University of Delhi)
• Inventors: Matapurkar, Balkrishna Ganpatrao
• Primary Examiner(s): Nguyen, Dinh X.
• Application Number:
  US08/921,307
• Time in Patent Office: 1,348 Days
• Field of Search: 128/898, 623/11.11, 623/23.64, 623/23.65, 623/23.66, 623/23.71, 623/23.72, 623/23.76
• US Class Current: 128/898
• CPC Class Codes: A61F 2/04 Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts A61F2/18, A61F2/20 take precedence; devices, other than stent-grafts, providing patency to, or preventing collapsing of, tubular structures of the body other than stent-grafts, e.g. stents A61F2/82; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95
• CPC Class Codes: A61F 2/042 Urinary bladders
• CPC Class Codes: A61K 35/545 Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells

Abstract

An in vivomethod of organogenesis of various tissues and/or organs in a mammalian body, comprising surgically transferring autogenous peritoneum containing stem cells to a place in the body where the desired tissue or organ is to be regenerated or repaired.

Claims

1. An in vivo and in situ method of organogenesis of various tissues or organs in a mammalian body, comprising steps of surgically transferring an autogenous peritoneal segment containing stem cells, said segment being selected from a corresponding contiguous embryonal region of the body that is away from the site where the organ or tissue is to be regenerated and providing a new functional need and a new tissue environment for regeneration of the desired tissue or organ.

2. A method as claimed in claim 1, wherein organogenesis of various tissues or organs involves repair or regeneration of such tissues or organs.

3. A method as claimed in claim 1 wherein the autogenous peritoneum is shifted by surgical technique to provide the proper cell movements to the desired site for regeneration of required tissue or/organ.

4. A method as claimed in claim 1 wherein the peritoneum used is a single stem celled layer on a basement membrane.

5. A method as claimed in claim 1, wherein an intrinsic factor such as messenger gene and genetic factor, inherent in the stem cells is exploited for the regeneration of the required tissue or organ.

6. A method as claimed in claim 1 which includes creating a stress of new functional need of a tissue system of new location to which the stem cells have been shifted, to induce desired metaplasia.

7. A method as claimed in claim 1 wherein a peritoneal layer is exclusively peritoneal membrane devoid of any muscle or fascia.

8. A method as claimed in claim 1 wherein the organ or tissue to be regenerated is selected from the group consisting of ureter, fallopian tube, uterus, uro-rectal septum, urethra, trigone and aponeurosis.

9. A method as claimed in claim 1 wherein the organogenesis or various tissues or organs incorporates functions of tissue inducers and/or tissue organizers to achieve regeneration/repair of any tissue or organ into its proper size, shape and form to perform its inherent function.

10. A method as claimed in claim 1 wherein a serosal surface of peritoneum is kept towards a lumen of the organ to be regenerated or repaired.

11. A method as claimed in claim 1 wherein a time period of 2 to 5 months is provided for the regeneration of organs or tissues from a grafted peritoneum.

12. A method as claimed in claim 1 wherein the organ is ureter a which is regenerated from a free peritoneal tube graft obtained from infra umbilical region just anterior to caecum and ascending colon extending downwards towards pelvis.

13. A method as claimed in claim 12 wherein cut ends of the ureter are spatulated before anastomosis with free ends of a peritoneal tube graft.

14. A method as claimed in claim 13 wherein a support is placed inside a free peritoneal graft tube to counter act abdominal pressure exerted on retro-peritoneal space.

15. A method as claimed in claim 12 wherein a support stent which is a tubular structure having a blunt-closed end placed towards a kidney and having an opening just below the blunt end, and an open end towards a urinary bladder is used to discharge the urine in the bladder, and the stent has perforations on side walls used to permit urine to come in contact with a graft and to allow excess urine to return back to a stent cavity.

16. A method as claimed in claim 12 wherein regeneration of ureter occurs in 2 to 5 months period.

17. A method as claimed in claim 12 wherein the regeneration of ureter occurs due to new functional need to which the stem cells of the free peritoneal graft is subjected to.

18. A method as claimed in claim 12 wherein the regeneration of the ureter from a peritoneal membrane graft occurs due to new tissue environment of the urinary tract.

19. A method as claimed in claim 1 wherein the organ to be regenerated is a fallopian tube which is being regenerated from a free peritoneal tube graft obtained from pelvic and posterior abdominal wall region.

20. A method as claimed in claim 19 wherein a stent is placed inside a free peritoneal graft tube as a support.

21. A method as claimed in claim 20 wherein the stent which is placed as a support passes through a uterus into a vagina and is secured into a vagina.

22. A method as claimed in claim 19 wherein the regeneration of fallopian tube takes place in 2 to 5 months time.

23. A method as claimed in claim 19 wherein cilia formation is observed in the inner layer of the regenerated fallopian tube and such formation is enhanced by the administration of a hormone such as estrogen in a manner known per se.

24. A method as claimed in claim 19 wherein the ends of the tubular graft and the fallopian tube are spatulated before anastomosis to avoid constriction at the anastomosed site.

25. A method as claimed in claim 1 wherein the organ to be regenerated is a uterus, a donor peritoneum being selected from pelvic peritoneum posterior to uterus extending on to the posterior abdomenal wall.

26. A method as claimed in claim 25 wherein a suitable support or stent being kept inside a tubular graft of the uterus preventing collapse of a grafted tube.

27. A method as claimed in claim 25 wherein the uterine artries on either side of the uterus are preserved and kept intact to provide blood supply to the unexcised part of the uterus.

28. A method as claimed in claim 25 wherein the duration of regeneration of uterus is from 2 to 5 months.

29. A method as claimed in claim 1 wherein the organ to be regenerated is uro-rectal septum for interpositional purpose, a peritoneal graft is selected from pelvic and parietal peritoneum.

30. A method as claimed in claim 1 wherein organs to be regenerated is urethra, the peritoneal graft for urethroplasty is selected from retrovescical peritoneum extending on posterior abdominal wall.

31. A method as claimed in claim 29 wherein two flaps of the size depending upon the distance of the defective site in pelvis from the anterior abdomenal wall, are obtained from parietal peritoneum and brought down in an abdomino-perineal tunnel which is surgically created to facilitate the repair, one of said flaps being used to cover the required defects of the rectum and/or vagina and the other of said flaps is being used to cover the repaired defect of urinary bladder and urethra.

32. A method as claimed in claim 29 wherein abdomino-perineal tunnel is created in male human being by providing inverted V-shaped incision to afford more space for deep dissection and to safeguard anal sphincter.

33. A method as claimed in claim 29 wherein a abdomino-vaginal tunnel is created in female human being by providing incision in the vagina and there by creating a space between urethra and anterior vaginal wall.

34. A method as claimed in claim 1 wherein the organ to be regenerated or repaired is a trigone, urethrial reconstruction or urethero plasty is performed employing the free peritoneum from retrovesiular pelvic and posterior abdomenal wall.

35. A method as claimed in claim 29 wherein the visceral aspect of peritoneum is placed towards the part to be regenerated or repaired in uro-rectal spetum.

36. A method as claimed in claim 30 wherein the visceral aspect of the peritoneum is placed towards the urethral lumen.

37. A method as claimed in claim 1 wherein the organs to be regenerated is aponeurosis which is regenerated from the peritoneal graft obtained from anterior abdominal wall developed from corresponding somite division.

38. A method as claimed in claim 37 wherein the regeneration occurs in 3 to 5 months period.

39. A method as claimed in claim 37 wherein the regenerating aponeurosis is being subjected to the pull and drag due to muscular activity of the abdominal muscles, abdominal distension, constant movements of the abdominal wall due to respiration, in order to impart the required strength to the regenerating aponeurosis.