The Experimental Studies And Clinical Application Of Transplantation Of Microencapsulated Bovine Chromaffin Cell For Pain Treatment

The Experimental Study and Clinical Application ofTransplantation of Microencapsulated BovineChromaffin Cell for Pain TreatmentDifferent extant of chronic pain may appear in majority of malignancy patients in their advanced stage, and the intractable pain in part of the patients seriously affects their quality of life. It was discovered that transplants of adrenal chromaffin cells into spinal subarachnoid space can produce obvious analgesic effect in recent years. In our study, bovine adrenal chromaffin cells were microencapsulated and the effect of Cryopreservation on morphology and function of the microencapsulated bovine chromaffin cells (BCC) were observed. In animal experiment, the effects of microencapsulated BCC on 2 pain models were studied. The effect of microencapsulated BCC as well as Fuzheng Chinese traditional medicine on advanced malignancy patients with intractable pain were observed in clinical trials.BCC were isolated by collagenase and then microencapsulated with Alginate-Polylysine-Alginate (APA). Microencapsulated BCC were cryopreserved with Dimethyl Sulfoxide, cryopreservative agent, and lowered temperature gradually. In resuscitating the cryopreserved cuvettes were plunged promptly into 37癈 water bath. The function and viability of microencapsulated BCC was assesd in vitro to observe then" ability in secreting basic catecholamines and the catecholamines secretion stimulated by K+ (58mmol/L) and acetylcholine (lO^mmol/L). Sciaticnerve ligation and formalin pain models were established and divided into 4 groups: groups of transplanting into subaracnoid space with microencapsulated BCC, naked BCC, empty microcapsule and NS respectively. The behavior changes of rats with Sciatic nerve ligation after cold and hot as well as that in the rats of formalin pain model after formalin injection were recorded. Microencapsulated BCC were transplanted into subarachnoid space of the patients with advanced malignancy suffering from intractable pain. Fuzheng Chinese drug was administrated in part of the patients as well and their changes of pain and qualify of life were observed.The morphology of microencapsulated BCC was not changed after cryopreservation, and both basic and stimulating cetecholamine secretion did not decrease significantly (P>0.05). In sciatic nerve ligated rats, by stimulation of cold or hot, the difference score of hind paw withdrawal frequency and cumulative duration in microencapsulated BCC group decreased significantly (P<0.05), while the decrease in naked BCC group was maintained only 2 weeks, and there was no difference between the empty microcapsule and NS group. The similar results were found in formalin pain model with formalin stimulation, hi the clinical trials, all of the 34 patients had pain relief and improved qualify of life rapidly after transplantation of microencapsulated BCC. The rate for pain relief was 82%. The longest pain relief time was maintained up to 150 days. Narcotic dosage was reduced or stopped in some patients. The pain relief in patients who administered Chinese drug in combination with transplantation of microencapsulated BCC was no significant difference compared with those received transplants only (P>0.05), but the qualify of life of former was superior to the later.In conclusion, it is demonstrated that: 1. Bovine chromaffin cells microencapsulated with APA technology can secret neuroactive substance normally and Cryopreservation does not affect the function of microencapsulated BCCsignificantly; 2. Microencapsulated BCC can play an analgesic role in xenogenic animal. 3. Microencapsulated BCC xenotransplantation provides a safe and effective approach for treatment of intractable pain in patients with advanced malignancy and improves their qualify of life. Although Fuzheng Chinese drug has no analgesic effect, but it may ameliorate patient's qualify of life.