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Examples of Fetal Cell Transplantation
Posted on: November 30, 2007

Fetal cells are the cells used to treat multiple disorders. These days due to ethical issues fetal cells can not be taken as a norm. Cord blood is an alternative of the fetal cells as it has many similarities with fetal cells. Here we show few examples of fetal cell treatment, which may be similar for cord blood cells.

In mammalian ontogeny, the liver constitutes the primary hematopoietic organ for some time. Fetal liver cells (FLC) are rich in hematopoietic stem cells with a high proliferative potential but contain few post-thymic T cells. In animal studies, FLC restored hematopoiesis without severe graft-versus-host disease. However, genetic disparity between donor and host frequently limited durable engraftment and prevented or protracted complete immune reconstitution in most fully allogeneic recipients. Some children with severe combined immunodeficiency have been cured by FLC infusion, whereas favorable effects in aplastic anemia, acute leukemia, and inborn errors of metabolism have been limited and badly understood. Fetal liver transplantation in animals may serve as a model for the analysis and management of complications associated with the transfer of purified hematopoietic stem cell grafts and aid in the development of future therapeutic strategies requiring rapidly proliferating stem cell populations.

2 patients with acute leukaemia in relapse were transplanted with fetal liver cells following a conditioning regimen of cyclophosphamide (120 mg/kg) and total body irradiation (1000 r). Each patient achieved a remission with haematopoietic recovery that was rapid in one case and delayed in the other. In one case there was evidence of chimerism as demonstrated by the presence of the XYY karyotype of the donor fetus in 20% of marrow metaphases, by the presence of double Y bodies in the peripheral blood, by the appearance of new HLA-antigens, and by red cell isoenzyme phenotypes of donor origin. In the second case there was prompt haematopoietic recovery and the appearance of red cell isoenzyme phenotype of donor origin. Survival was 153 and 30 days respectively, and both patients died of interstitial pneumonia without evidence of graft versus host disease.

40 patients with severe aplastic anaemia received an intravenous infusion of 0.004 to 11.1 · 108 (median: 8 · 108) hematopoietic cells prepared from the fetal livers of 8-32 week old abortuses. Median survival of responders was 15.7 months. The survival details are:

  • 5 patients, who died within 15 days of fetal liver infusion, are excluded from analysis.
  • 22 of the 35 evaluable patients (62%) responded favourably.
  • 6 of the 7 patients with good response were alive after 9 to 44 months (median: m = 20); one died 106 months after fetal liver infusion due to renal lithiasis.
  • 4 of the 7 patients with moderate response were alive after 9 to 31 months; 3 died within 16 months.
  • 7 of 8 patients with minimal response died in 3.4 to 10 months (m = 6); the 8th patient was lost to follow-up .

Bone marrow cellularity became normal in 12 patients following fetal liver infusion. In 7 patients there was a relapse; 6 regained a normal bone marrow cellularity after a second or third fetal liver infusion. These data strongly suggest a role of fetal liver infusion in inducing bone marrow recovery. Of 13 non-responders, 4 were lost to follow-up and 9 died within 20 days-4.3 months (m = 1.6). Fetal liver infusion appears to be an effective therapy in patients with severe aplastic anaemia.

The explants of two human fetal pancreases of 15 weeks gestational age were cultured for 6-7 days before being implanted in a 29-year-old insulin-dependent diabetic woman who had received a renal graft two months previously. One pancreas was placed in the flexor muscles of the forearm whilst the other was implanted in an omental pouch. To reduce the chances of rejection the tissue was cultured in vitro, the donor of the tissue placed in the forearm was DR antigen matched with the recipient and the patient remained on cyclosporin and prednisone therapy. At 3 months a mass developed in the forearm muscle at the site of transplantation, and continued to grow. Biopsy at 13 months showed a small area of original pancreas surrounded by a large collection of mature lymphocytes and fibrous tissue. A and D cells could be seen around pancreatic ducts but B cells and acinar tissue were absent. At no stage during follow-up was plasma C-peptide detected in the recipient.

Sources:
1. Prummer O, Fliedner TM.; The fetal liver as an alternative stem cell source for hemolymphopoietic reconstitution.Int J Cell Cloning. 1986 Jul;4(4):237-49.
2. Lucarelli G, Izzi T, Porcellini A, Delfini C, Galimberti M, Moretti L, Polchi P, Agostinelli F, Andreani M, Manna M, Dallapiccola B.; Fetal liver transplantation in 2 patients with acute leukaemia after total body irradiation.; Scand J Haematol. 1982 Jan;28(1):65-71.
3. Kochupillai V, Sharma S, Francis S, Nanu A, Mathew S, Bhatia P, Dua H, Kumar L, Aggarwal S, Singh S, et al.; Fetal liver infusion in aplastic anaemia.; Thymus. 1987;10(1-2):95-102.
4. Tuch BE, Sheil AG, Ng AB, Turtle JR.; Long-term survival of human fetal pancreatic tissue transplanted into an insulin-dependent diabetic patient.; Diabet Med. 1986 Jan;3(1):24-8.
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