Human fetal adrenal transplant: a possible role in relieving intractable pain in advanced rheumatoid arthritis

The art of transplant surgery has gone a long way in establishing itself as an important discipline in medicine with the support of molecular biology, immunology, biochemistry, etc., as the ultimate treatment for the restoration of function of a failing organ. With the progressive increase in the life expectancy of human beings, there is an increasing discrepancy in the demand and supply of organ grafts. A less efficient alternative could be synthetic or mechanical grafts. Nucleated cell therapy, that is, cellular transplant, is a promising new area of study with its proven efficacy in neuro-degenerative disorders, hematopoietic disorders, diabetes and trauma-induced tissue loss, to name a few. Human fetal cell/tissue with its intrinsic hypo-antigenic advantage (up to 20 weeks of study), could be an interesting area of cellular/tissue transplant. Our research group has earlier reported on the safe use of umbilical cord whole blood and the successful transplant of a human fetal lung, heart, pancreas, liver, thymus, in an artificially prepared vascular subcutaneous axillary fold in which there was no feature of hyper-acute, acute or chronic rejection of the graft in HLA- and sex-randomized adult recipients, without concomitant immunosuppressives or radiation of the host to potentiate the survival of the fetal graft (within 20 weeks of gestation) within the lowest observation period of one month. The present study was aimed at examining the role of developing fetal adrenal transplants for patients with rheumatoid arthritis and severe pain due to involvement of inflammatory and neuropathic components.

Ten cases were enrolled in the present study after thorough informed consent and approval by the ethical committee of the institute. The age of the patients varied from 50 to 76 years and the group was comprised of three males and seven females. The age of the adrenal grafts varied from 16 to 20 weeks and these were collected from mothers admitted for hysterotomy and ligation. These long-standing rheumatoid patients (suffering for five to 15 years), presented with at least four of the seven 1987 revised criteria of the American College of Rheumatology for diagnosis of rheumatoid arthritis. A 2.5 cm long and 2 cm deep tissue space was dissected and prepared in each transplant recipient at the axilla using diathermy and knife after infiltrating the site with one percent lignocaine solution. The tissue collected from the consenting mother undergoing hysterotomy and ligation was inserted into this site, and the site was closed with 00 atraumatic vicryl. All necessary pre- and postoperative surgical precautions were taken to prevent infections. Sequential total count and differential count of leucocytes were undertaken to analyze the impact of the transplant on the host. After one month, a part of the transplanted fetal tissue was recovered for histological staining to examine whether there was any graft versus host reaction.

All ten patients tolerated the transplant procedure well. There was no fever, intractable pain or any other specific serious side-effect which could justify the removal of the transplant before one month. There was no discharge from the incision site and the healing of the scar was by and large normal. There was no unusual leucocytosis, lymphocytosis and the retrieved graft tissue did not suggest transplant rejection. However, there was definite pain relief, reduction in swelling and improvement of mobility of varying degree in a majority of the patients which was perceivable from the 15th day onwards. There was also a sense of well being (in 80%) and a gain in weight of three pounds or more (in 70%) among the fetal transplant recipients.

To understand the underlying mechanism, in case of pregnancy immunotolerance, we are of the opinion that emphasis should be placed on the role of non-specific and non-cytopathic blocking antibodies produced during pregnancy. The hypo-antigenicity of the developing human fetal system may possibly contribute to the production of this blocking antibody during pregnancy, and thus may play a role in the lack of recognition by the host's HLA system. This behaviour of the developing human fetal tissue provides some advantages over adult tissue for fetal cell/tissue transplantation purposes. The relief of pain, inflammation and restoration of mobility may be due to the effect of the transplanted adrenal graft, with the medullary component contributing to endorphin-like substance liberation and the cortical component contributing to glucocorticoid synthesis.