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PubMed2004

Stem cell transplantation for autoimmune disorders. Coincidental autoimmune disease in patients transplanted for conventional indications.

The practice of stem cell transplantation for severe autoimmune diseases refractory to conventional therapy originated from two landmark discoveries: the excellent results of animal experiments, and serendipitous observations in human coincidental diseases. The latter include patients with an often long-standing autoimmune disease who have developed a haematological condition (aplasia, leukaemia, lymphoma) requiring stem cell transplantation (from marrow as well as from blood). Allogeneic and autologous transplants have been performed. The initial information deriving from both procedures is their feasibility, even more convincing since the patients were affected by two simultaneous severe diseases. The information derived from autologous transplants has, however, now been superseded by the considerable and increasing number of those transplants performed for primary autoimmune diseases. On the other hand, allogeneic stem cell transplantation for very severe autoimmune diseases is being cautiously explored in current protocols. Allogeneic transplants in coincidental disease have also suggested a graft-versus-autoimmunity effect, which may become relevant in conjunction with non-myeloablative, less toxic condition regimens.

Arthritis, Rheumatoid↗
PubMed1997

In utero hematopoietic stem cell transplants prolong survival of postnatal kidney transplantation in monkeys.

The authors hypothesized that in utero transplantation of T-cell-depleted paternal marrow into rhesus monkey fetuses would induce tolerance to postnatal kidney grafts from the marrow donor. T-cell-depleted paternal bone marrow was transplanted intraperitoneally into two female fetal rhesus monkeys at 61 +/- 1 days' gestation. Chimeric monkeys (n = 2) received kidney transplants from paternal donors. Control monkeys (n = 2) underwent kidney transplants without prior in utero stem cell transplants. Both chimeric monkeys demonstrated low level (<0.1% donor cells) engraftment in the bone marrow and peripheral blood using the polymerase chain reaction assay for the Y chromosome. The mixed lymphocyte reaction demonstrated hyporeactivity to the donor. Control animals demonstrated severe acute rejection and graft failure 1 week posttransplant. The first chimeric monkey had no significant clinical or sonographic evidence of renal failure until 7 weeks after the transplant. Biopsy findings showed mild rejection 1 week postoperatively, but rejection did not significantly progress until 5 weeks later. The second chimeric monkey had no significant clinical or sonographic changes for 4 weeks, but evidence of moderate rejection was seen on biopsy results. This monkey was given a 10-week course of immunosuppression, and had no clinical or sonographic renal deterioration, although biopsy results showed chronic rejection that was confirmed when electively euthanized 8 months later. Our data suggest that in utero transplantation of hematopoietic stem cells can increase the survival of a kidney allograft in the rhesus monkey.

Animals↗
PubMed1996

Randomised trial of filgrastim-mobilised peripheral blood progenitor cell transplantation versus autologous bone-marrow transplantation in lymphoma patients.

BACKGROUND: A randomised trial comparing filgrastim-mobilised peripheral blood progenitor cell (PBPC) transplants with autologous bone marrow transplantation (ABMT) for haematopoietic stem cell support has not been done. We compared the effects of filgrastim-mobilised PBPC or autologous bone marrow reinfused to lymphoma patients after high-dose chemotherapy in a prospective randomised multicentre trial. METHODS: The trial was done at six centres in three European countries. After high-dose chemotherapy (carmustine, etoposide, cytarabine, and melphalan [BEAM protocol]) 58 patients with advanced Hodgkin's disease or high-grade non-Hodgkin lymphoma received either filgrastim-mobilised PBPC (n = 27) or bone marrow (n = 31) for haemopoietic reconstitution. FINDINGS: The median number of days with platelet transfusions after grafting was 6 in the PBPC transplantation group and 10 in the ABMT group (estimate of treatment difference 5 days, 95% CI 3-7 days). Time to platelet recovery above 20 x 10(9)/L was 16 days in the PBPC transplantation group and 23 days in the ABMT group (p = 0.02). Time to neutrophil recovery above 0.5 x 10(9)/L was also reduced in the PBPC transplantation group (11 vs 14 days, p = 0.005). Patients randomised to PBPC transplantation needed fewer red blood cell transfusions (two vs three, p = 0.002) and spent less time in hospital (17 vs 23 days, p = 0.002). Early post-transplant morbidity and mortality as well as overall survival (median follow-up 311 days) were similar in both groups. There was no notable toxicity ascribed to filgrastim administration or the leucapheresis procedures. INTERPRETATION: In patients with lymphoma treated with high-dose chemotherapy, reinfusing filgrastim-mobilised PBPC instead of autologous bone marrow significantly reduced the number of platelet transfusions, the time to platelet and neutrophil recovery, and led to earlier discharge from hospital.

Adult↗
PubMed2002

Incidence of histoplasmosis following allogeneic bone marrow transplant or solid organ transplant in a hyperendemic area.

Questions have arisen regarding the risk of developing symptomatic Histoplasma capsulatum infection among patients who undergo transplant-related immunosuppression in areas endemic for histoplasmosis. Our medical center is located in a hyperendemic area for histoplasmosis, where three large outbreaks occurred since 1978. We undertook a retrospective chart review of 137 patients who received allogeneic bone marrow transplant and of 449 patients who received solid organ transplant from January 1994 to December 1996 in order to assess the incidence of active histoplasmosis. Charts were reviewed before and after transplantation for clinical outcomes, H. capsulatum serologies and antigen results, and microbiological and radiological results. After a mean follow-up duration exceeding 16 months, no patient was diagnosed with histoplasmosis. In the absence of an outbreak, histoplasmosis is a rare infection following the immunosuppression of allogeneic bone marrow or solid organ transplantation even in a hyperendemic area. Pre-transplant serologies or chest radiographs consistent with prior infection were not associated with post-transplant histoplasmosis.

Adult↗
PubMed2003

Immune reconstitution, infectious complications and post transplant supportive care measures after autologous blood and marrow transplantation in children.

We retrospectively analyzed data on T- and B-cell reconstitution and infectious complications in 58 children undergoing ABMT, in order to evaluate post-transplant supportive care measures used during the study period. Normalization of T-cell number and lymphocyte proliferative responses to phytohemagglutinin (PHA) and alloantigen (MLC) occurred in two-thirds of children by 6 months post transplant. Normal IgM levels developed in 75% of children by 6 months post transplant. A total of 34 children (59%) developed 39 episodes of infection between neutrophil engraftment and 1 year post transplant. The most common infections included bacteremia, varicella-zoster virus infection and pneumonia, which represented 46, 23 and 9% of infections, respectively. All patients with bacteremia had a central venous catheter in place at the time of infection. Most infections (77%) developed by 6 months post transplant. In this small patient cohort, time to normalization of tests of T- and B-cell function was not significantly different between patients with and without infection. Earlier removal of an indwelling central venous catheter may decrease the risk of bacteremia post transplant. Post-transplant supportive care measures may be discontinued at 6 months post ABMT in most children, as the risk of infection decreases after that time.

Adolescent↗
PubMed2002

Factors affecting long-term outcome after allogeneic haematopoietic stem cell transplantation for acute myelogenous leukaemia: a retrospective study of 172 adult patients reported to the Austrian Stem Cell Transplantation Registry.

Between 1982 and 2000, 172 patients with acute myelogenous leukaemia (AML) received haematopoietic stem cell transplants (SCT) from related (n = 132) or unrelated (n = 40) donors at four Austrian transplant centres and their results were reported to the Austrian Stem Cell Transplantation Registry. Conditioning for SCT consisted of cyclophosphamide and total body irradiation in 156 (91%) patients. Graft-versus-host disease (GVHD) prophylaxis was with standard cyclosporine and methotrexate in 95 (55%) patients. Median post-transplant follow-up was 5.6 years (range, 0.2--16.7). Multivariate analysis of transplant-related mortality (TRM) identified four variables associated with a lower risk: disease status of first complete remission (CR) at SCT, patient age of 45 years and younger, transplant performed during or after 1995, and lack of acute GVHD. Variables associated with significantly improved leukaemia-free survival were: bone marrow as the stem cell source, disease status of first CR at SCT, and occurrence of chronic GVHD. In multivariate analysis, transplantation performed during or after 1995, first CR at SCT, occurrence of limited chronic GVHD and lack of acute GVHD grades III to IV were associated with increased overall survival. Based on these analyses, options for the improvement of results obtained with allogeneic SCT in patients with AML could be defined.

Adult↗
PubMed2003

Amount of co-transplanted donor-derived leukocytes determines in-vivo microchimerism and mixed lymphocyte culture changes post-liver transplantation.

OBJECTIVE: To evaluate the impact of passenger leukocytes in liver grafts on the rate of microchimerism induction after liver transplantation and to evaluate immunological changes thereafter based on serial donor-specific MLC's in these patients. METHODS: 26 orthotopic liver transplant recipients were prospectively evaluated for immunological changes based on the co-transplantation of donor-derived leukocytes. Intraoperatively harvested liver biopsies and peripheral blood-lymphocytes of liver transplant recipients were sampled at various time points. Donor spleen cells were obtained during organ procurement. RESULTS: HLA-PCR analysis demonstrated a stable pattern of microchimerism in 15 out of 26 patients. Microchimerism was detectable by PCR up to a mean of 7 weeks after transplantation, when chimerism in the peripheral blood became negative. Passenger donor leukocytes were present in all biopsies obtained during backtable preparation of the liver graft. For the 15 patients presenting microchimerism the rate of passenger leukocytes in the liver graft biopsies showed a mean of 155.8 leukocytes per mm 2 liver tissue (SD +/- 23.2 cells/mm2, range 121 to 217 cells per mm2 tissue). Otherwise patients without chimerism showed a mean of 90.4 passenger leukocytes per mm2 tissue (SD +/- 14.5 cells/mm2, range: 52 to 99 cells/mm2). Lymphocyte proliferation, determined by donor-specific "multiple" single-way- mixed-lymphocyte-cultures (dsmMLC) was reduced to a mean of 62.2 % of preoperative values (SD +/- 14.5 %, range 33 % to 88 %) in the 15 patients with stable microchimerism. Otherwise in the 11 patients without microchimerism dsmMLC results stayed at continuously higher levels with a mean of 106 % (SD +/- 13.4, range 92 % to 134 %). CONCLUSIONS: The results from these studies of microchimerism and lymphocyte reactivity after liver transplantation suggest that the co-transplantation of donor leukocytes plays an important and active role in the modulation of the host-immune system.

Biopsy, Needle↗
PubMed2003

Immunological and clinical effects of post-transplant G-CSF versus placebo in T-cell replete allogeneic blood transplant patients: results from a randomized double-blind study.

BACKGROUND: Immunological and clinical effects of post-transplant growth factor administration have not been well studied. This report describes the outcome and immune functions of a total of 50 HLA-matched related donor allogeneic blood stem-cell transplantation patients who received post-transplant G-CSF (10 microg/kg) or placebo. METHODS: Immune status, including number of lymphocyte subsets and their functions, and serum immunoglobulin levels and clinical status--including GvHD, rate of relapse, event-free survival, and overall survival--were determined in the patients enrolled in this study. RESULTS: Twenty-eight patients survived 1 year after transplant, and 15 patients had available results to compare immune function by randomization assignment. At 12 months post-transplant, immune parameters in G-CSF versus placebo groups showed no statistically significant differences in number of circulating lymphocyte subsets CD3, CD4, CD8, CD19 and CD56 in the two groups. There was no significant (NS) difference in immunoglobulin IgG, IgA and IgM levels, NK or LAK cell-mediated cytotoxicity levels, and mitogen-induced proliferation between post-transplant G-CSF and placebo group. In addition, the analyses of immune parameters at earlier time-points on Days 28, 100, 180, and 270 revealed that, except for LAK cytotoxicity at Day 100, there was no differences between the two groups. Fourteen of 26 patients are alive in the G-CSF arm and nine of 24 in the placebo arm. Median follow-up of surviving patients is 43 months. Four year overall and event-free survival in the G-CSF and the placebo group were 53% and 35% (NS), and 44% and 36% (NS) respectively. Bacterial or fungal infections were the cause of six of 12 deaths in the G-CSF arm (all bacterial) and of four of 15 deaths in the placebo arm (two deaths from Aspergillus) (P=0.26). Two patients relapsed in the G-CSF arm and three in the placebo arm. Four year cumulative incidences of relapse were 8% versus 13% in G-CSF versus placebo arms, respectively, (NS). Chronic GvHD developed in 14 of 19 100-day survivors after G-CSF (11 extensive stage), and in 17 of 20 (14 extensive stage) in the placebo arm. The 4-year cumulative incidence of chronic GvHD was 56% [95% confidence interval (CI) 24-88%] after G-CSF and 71% (95% CI 48-94%) after placebo; this difference was not statistically significant (log rank P=0.41). CONCLUSION: In summary, there were no significant immunological or alterations in clinical benefit of post-transplant G-CSF administration in T-replete allotransplant recipients.

Adult↗
PubMed2003

Biological aspects of limb transplantation: I. Migration of transplanted bone marrow cells into recipient.

The transplanted limb contains bone marrow tissue. The hematopoietic cells contained in the bone of the graft normally differentiate after transplantation and can be released to the recipient. The cells migrate to the recipient bone marrow cavities and lymphoid organs. This causes the immune reaction between the donor and the recipient, which develops not only in the graft itself but also in the recipient immune organs where donor bone marrow cells home. The purpose of this study was to investigate the process of migration of the hematopoietic cells from the donor limb to the recipient bone marrow cavities and lymphoid tissues. The questions the authors asked were: what is the rate of release of bone marrow cells from the transplanted bone, where do the released bone marrow cells home in the recipient, how fast are donor bone marrow cells rejected by the recipient, and can some bone marrow cells homing in the recipient tissues survive and create a state of microchimerism. Experiments were performed on Brown Norway and Lewis inbred rat strains (n = 30). Limb donors received intravenous chromium-51-labeled bone marrow cells. Twenty-four hours later, the limb with homing labeled bone marrow cells was transplanted to an allogeneic or syngeneic recipient. The rate of radioactivity of bone marrow cells released from the graft and homing in recipient tissues was measured after another 24 hours. To eliminate factors adversely affecting homing such as the "crowding effect" and allogeneic elimination of bone marrow cells by natural killer cells, total body irradiation and antiasialo-GM1 antiserum were applied to recipients before limb transplantation. In rats surviving with the limb grafts for 7 and 30 days, homing of donor bone marrow cells was studied by specific labeling of donor cells and flow cytometry as well as by detecting donor male Y chromosome. The authors found that transplantation of the limb with bone marrow in its natural spatial relationship with stromal cells and blood perfusion brings about immediate but low-rate release of bone marrow cells and their migration to recipient bone marrow and lymphoid tissues. Large portions of allogeneic bone marrow cells are rapidly destroyed in the mechanism of allogeneic elimination by radioresistant but antiasialo-GM1-sensitive natural killer cells. Some transplanted bone marrow cells remain in the recipient's tissues and create a state of cellular and DNA microchimerism. A low number of physiologically released donor bone marrow cells do not seem to adversely affect the clinical outcome of limb grafting. Quite the opposite, a slight prolongation of the graft survival time was observed.

Animals↗
PubMed1984

Physiologic aspects of human heart-lung transplantation. Pulmonary function status of the post-transplanted lung.

Pulmonary function measurements were performed before and after heart-lung transplantation in nine patients who had undergone surgery for end-stage pulmonary hypertension. In seven of them, sequential follow-up studies were performed at variable times postoperatively with the longest period 27 months. Pre-transplant studies showed a mild restrictive defect in 33 percent and obstructive disease in 50 percent of the patients, respectively. Arterial hypoxemia was present in all patients. The degree of mechanical changes found did not appear severe enough to account for the marked dyspnea and disability characterizing this group of patients with pulmonary hypertension. Following transplantation, all patients showed striking improvement of symptoms and general physical status. In the early post-transplant period, there was a marked decrease in most lung volumes resulting in a moderately severe restrictive ventilatory defect. Flow parameters that were reduced could be related to decreased volumes and not to intrinsic airway obstruction. Arterial O2 tensions improved dramatically and gas exchange was maintained at essentially normal levels. Lung function tended to improve progressively following transplantation with the passage of time. Heart-lung transplant is consistent with an adequate long-term pulmonary functional state which has the capacity to sustain the normal activities of daily living. From the standpoint of lung function, heart-lung transplantation appears to be acceptable as a form of therapy in selected patients.

Adult↗
PubMed2006

High-dose therapy and autologous hematopoietic stem cell transplantation for patients with primary systemic amyloidosis: a Center for International Blood and Marrow Transplant Research Study.

OBJECTIVE: To determine the outcome of high-dose therapy with autologous hematopoietic stem cell transplantation (HSCT) in patients with primary systemic amyloidosis reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). PATIENTS AND METHODS: A total of 107 recipients of autologous HSCT for amyloidosis from 48 transplantation centers were reported to the CIBMTR between 1995 and 2001. Hematologic and organ responses were assessed at 100 days and 1 year. Transplantation-related mortality (TRM) was assessed at day 30 after HSCT. A multivariate analysis assessed factors that influenced overall survival. RESULTS: Improvement at day 100 was seen in 1 or more amyloidosis-affected sites (bone marrow, kidney, liver, and/or heart) in 28 (36%) of 77 patients; the 1-year responses included complete response (16%), partial response (16%), stable disease (31%), and disease progression (10%). With a median follow-up of 30 months, the 1- and 3-year survival rates were 66% (95% confidence interval [CI], 56%-75%) and 56% (95% CI, 45%-66%), respectively. The day 30 TRM was 18% (95% CI, 11%-26%). In the multivariate analysis, only the year of transplantation (patients who most recently underwent transplantation) was associated with post-HSCT survival (P-.02). CONCLUSION: In this multi-institutional CIBMTR study, the 3-year survival rate was comparable to single-center results, with patients who more recently underwent transplantation faring better. Of note, the TRM was higher than that reported by single centers, which may reflect differences in patient selection and/or experience in treating this challenging disease. We hope that a better understanding of the recently recognized prognostic factors and more stringent patient selection will result in lower TRM and improved survival.

Adult↗
PubMed1999

[Reconstitution of peripheral blood lymphocytes in patients treated with bone marrow transplantation: comparison between allogeneic and autologous transplantation].

BACKGROUND: This study compares the immune reconstitution of total T cells, CD4 and CD8 cell subsets, activated T cells, NK cells and B cells in 66 patients who underwent allogeneic or autologous bone marrow transplantation (BMT). PATIENTS, MATERIAL AND METHODS: The reconstitution of peripheral lymphocytes subsets was studied using two-color flow cytometry. The study group consisted of 39 patients who received allogeneic BMT compared with 27 patients who received autologous BMT. Peripheral blood was examined at different time intervals. As a measure of immune function, the response to the mitogen phytohemaglutinin (PHA) was determined. RESULTS: The pattern of recovery of CD3+, CD4+ and CD8+ T cells, as well as the PHA response, was similar for each type of transplant. CD3+CD5- cells were significantly higher following autologous BMT than after allogeneic BMT and during more time. An overexpression of DR on T cells following autologous or allogeneic BMT demonstrates an increasing degree of T-lymphocyte activation. This activated T-cell subset was more stable in patients transplanted with allogeneic BM than in patients treated with autologous BM. The levels of total B cells and CD19+CD5+ B-cells were increased during 2 to 12 months following autologous MBT, remaining normal afterwards; in contrast, the levels of CD19+ lymphocytes and CD19+CD5+B-cells remained higher than normal ranges until 36 months in patients transplanted with allogeneic BM. The percentage of NK cells was significantly increased following both autologous and allogeneic BMT. The highest percentage of NK cells were detected about 2 and 6 months post-transplant in patients treated with autologous or allogeneic BM, respectively. CONCLUSIONS: Allogeneic BMT appears to induce a slight delay recovery of B and NK cells in comparison to autologous BMT. In contrast, T-cells recovery was similar for each type of transplant, although a higher percentage of CD3+CD5- T cells and a faster recovery of activated CD3+DR+ cells to normal levels were observed in patients transplanted with autologous BM.

Adolescent↗
PubMed2003

[Tolerance in transplantation: potential contribution of haematopoietic transplantation and cell therapy].

The ultimate objective of organ transplantation is to obtain a state of tolerance, i.e. long-term acceptance of the graft without immunosuppressive therapy in order to limit the complications of these treatments (viral infections, tumours, etc.). The various immunological mechanisms allowing a state of tolerance will be described in this review. Among these various experimental strategies, combined bone marrow (or haematopoietic stem cell) transplantation and organ transplantation, made possible by the development of non-myeloablative or less intensive conditioning, appears to be one of the most promising lines of research. This approach leads to colonization of the recipient by donor cells. This state is described as "macro-chimerism" and achieves a real state of central tolerance in relation to an organ derived from the bone marrow donor. We have shown recently that intravenous injection of apoptotic cells in combination with allogeneic bone marrow cells increases the success rate of bone marrow transplantation. In a model of combined bone marrow/solid organ transplantation, these apoptotic cells induce tolerance limited to the donor's bone marrow cell antigens without inducing auto-immunization. We therefore propose a new approach to cell-based therapy (using the immunomodulating properties of apoptotic cells) to promote the success of haematopoietic stem cell transplantation. This approach can be particularly useful in combined haematopoietic stem cell and organ transplantation in order to induce a state of macro-chimerism.

Animals↗
PubMedDate not supplied

Effect of simultaneous lung transplantation on heart transplant survival in rats.

Clinical observations in humans reveal that heart-lung transplant recipients suffer significantly less cardiac rejection than those receiving only heart transplants. A heterotopic combined heart-lung model in rats was used to test the hypothesis that the presence of the lung in this combination increases survival of the heart transplant. Cardiac survival was compared between en bloc heart-lung transplants and heart transplants. Low dosages of cyclosporine were used to prolong but not prevent the rejection process. Heart graft survival in the cyclosporine, 1 mg/kg/day, groups was significantly prolonged in heart-lung allografts. Histologic studies also demonstrated more advanced rejection of the heart in the heart-only transplant groups as compared with the heart-lung transplant groups. This study shows that the presence of the lungs in heart-lung allografts provides for prolongation of cardiac survival.

Animals↗
PubMed1977

[Experimental and clinical aspects of the living articular cartilage transplantation and half-joint transplantation (author's transl)].

The articular cartilage transplantation and the half-joint transplantation necessitate the assessment of specific biological-transplantation questions as to the structure and function of the hyaline cartilage. Compared with other organ transplantations biometric and biomechanical factors have to be taken into consideration additionally. Up to now contradictory results were obtained in the animal experiment. On principle a survival of grafted non-preserved parts of cartilage seems to be possible. In clinical practice therapeutic trials for autogenous reimplantation of articular cartilage, autogenous joint surface partial transplantations and half-joint transplantations are justified. Allogenous half-joint transplantations may also be possible in exceptional cases.

Adolescent↗
PubMed1981

[Effect of different transplant conditions on lipid peroxidation in the transplant and the recipient's tissues].

This work analyses the change of LPO intensity in transplanted skin and in recipient tissue: in blood and skin adjoining the transplants during 27 days after auto- and homotransplantation. A conclusion is made that primary LPO strengthening of autotransplants and skin, adjoining the transplant during 9-14 days after transplantation, growing lesser, reaches the level of intact skin. Under homotransplantation the primary LPO strengthening not only reaches the initial level 9-14 days of the transplantation, but continues to increase. It was shown that the first maximum of LPO strengthening in the transplants (2-5 days after transplantation) were caused by ischemic lesions and the second maximum - by immunologic shifts.

Animals↗
PubMed1994

[Humoral immunity and infections during bone marrow transplantation in children: study of 127 transplanted patients successively in a same center].

BACKGROUND: Children with malignant diseases are frequently given high dose chemotherapy plus autologous bone marrow transplants. Infectious complications can lead to morbidity and mortality in this type of treatment. This study was designed to determine whether immunoglobulin deficiency is an additional risk factor for infections. PATIENTS AND METHODS: One hundred and twenty seven children with solid malignant tumors were treated between November 1987 and April 1992 in our Department by chemotherapy followed by autologous bone marrow transplantation. Their serum IgA, IgG and IgM concentrations were measured by nephelometry before chemotherapy, on the day of transplantation and every week thereafter. The frequency and severity of infectious episodes in all the children were recorded using a standard scale. The patients were divided into two subgroups, defined according to their serum IgG concentrations before the transplantation and 7 and 21 days later. RESULTS-Ig deficiency during transplantation was not associated with the occurrence of septicemia or focal infections. It was associated with the course of infection (P = 0.003) and with the occurrence of zoster virus infection during the first 6 months after transplantation (P = 0.003). CONCLUSIONS: Immune replacement during bone marrow transplantation may be indicated in children at risk of Ig deficiency. Fifty percent of the children with solid tumors treated in our institution were at risk of this deficiency.

Adolescent↗
PubMed1982

Transplantation of tectal tissue in rats. III. Functional innervation of transplants by host afferents.

Fetal tectal tissue was transplanted adjacent to the superior colliculus of neonatal rats. In mature recipient animals, ultrastructural studies provided evidence of host cortical synapses on cells within the transplants. To determine whether these synapses were functionally effective in driving transplant cells, tungsten in glass microelectrodes were used to record from single units in the transplants and the host cerebral cortex was electrically stimulated. Of the 214 tested units which were shown histologically to be within the transplants, 25 (11.7%) were orthodromically excited from host cortex at latencies of 15 ms or less (mean 7.3 ms). A further four transplant units were activated at relatively long latencies (40-300 ms). The presence of a functional host retinal input was also tested by electrically stimulating the host optic nerves. No transplant units were activated from these sites, apparently because very few electrode penetrations passed through the localized zones of optic axon distribution. The possible functional interrelationships between transplant and host are discussed.

Animals↗