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Autologous Transplantation (autologous + transplantation)
Selected AbstractsInsulin-Producing Cells Derived from Rat Bone Marrow and Their Autologous Transplantation in the Duodenal Wall for Treating DiabetesTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 5 2009Yu-Hua Zhang Abstract Islet cell transplantation is one of the most promising therapies for diabetes mellitus (DM). However, the limited availability of purified islets for transplantation and the risk of immunological rejection severely limit its use. In vitro transdifferentiation of autologous bone marrow-derived mesenchymal stem cells (BMSCs) into insulin-producing cells (IPCs) could provide an abundant source of cells for this procedure and avoid immunological rejection. Here, we isolated and characterized BMSCs and induced their in vitro differentiation into IPCs. Reverse-transcription polymerase chain reaction analysis revealed that these IPCs could express Ins1, Ins2, glucagon, glucose transporter 2, and pancreatic duodenal homeobox-1. Insulin production by the IPCs was confirmed by immunocytochemistry and Western blot analysis. On this basis, donor rats supplying BMSCs were made diabetic by a single intraperitoneal injection of streptozotocin. The IPCs were then autologously transplanted into the duodenal submucosa of diabetic rats. Grafted cells could be visualized in sections after 2, 4, and 8 weeks by immunohistochemical staining for insulin. Furthermore, in the IPC-implanted group, hyperglycemia was normalized, compared with a persistent increase in glucose levels in the diabetic group and intraperitoneal glucose tolerance test-induced responses were observed in the IPC-implanted group. These results on autologous transplantation of IPCs derived from BMSCs into the duodenal wall could offer a novel potential therapeutical protocol for DM. Anat Rec, 292:728,735, 2009. © 2009 Wiley-Liss, Inc. [source] Autologous Transplantation of Fascia into the Vocal Fold: Long-Term Result of Type-1 Transplantation and the Future,THE LARYNGOSCOPE, Issue S108 2005Koichi Tsunoda MD Abstract Objectives: Since 1997, we have performed the autologous transplantation of fascia into the vocal fold (ATFV) procedure on cases of sulcus vocalis. In what follows, we report the long-term results of our new surgical approach and discuss the role of these transplantations. We also review and report some complications that can be caused by ATFV. Finally, we discuss the ATFV technique as a contribution to the phonosurgery of the future. Study Design: Prospective study. Methods: We were able to obtain long-term results from 10 volunteer cases (2 female and 8 male, age: 15,71, mean 46.5 years old) who could be followed up for at least 3 years after transplantation. All were cases of pathologic sulcus vocalis. We measured maximum phonation time (MPT) and carried out pre- and postsurgical clinical observation and laryngeal stroboscopy in all cases. These measurements and observations were made before the ATFV and at 6 months, 1 year, 2 years, and 3 years after surgery. Results: In stroboscopic observation 1 year after the ATFV, satisfactory glottal closure and excellent mucosal wave were observed for all cases, and there was no case with hyperadduction of the false vocal folds. MPT measures remained at an improved level 2 years and 3 years after the transplantations. Paired-sample t tests showed that the improvement relative to preATFV levels was significant for all postsurgical measurements up to 3 years. Conclusions: We conclude that ATFV is a successful surgical procedure for sulcus vocalis and scarred vocal folds. Other phonosurgical clinical applications may also be envisioned. [source] Human Islet Isolation for Autologous Transplantation: Comparison of Yield and Function Using SERVA/Nordmark Versus Roche EnzymesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2009T. Anazawa Islet autotransplantation (IAT) is used to preserve as much insulin-secretory capacity as possible in patients undergoing total pancreatectomy for painful chronic pancreatitis. The enzyme used to dissociate the pancreas is a critical determinant of islet yield, which is correlated with posttransplant function. Here, we present our experience with IAT procedures to compare islet product data using the new enzyme SERVA/Nordmark (SN group; n = 46) with the standard enzyme Liberase-HI (LH group; n = 40). Total islet yields (mean ± standard deviation; 216 417 ± 79 278 islet equivalent [IEQ] in the LH group; 227 958 ± 58 544 IEQ in the SN group; p = 0.67) were similar. However, the percentage of embedded islets is higher in the SN group compared to the LH group. Significant differences were found in pancreas digestion time, dilution time, and digested pancreas weight between the two groups. Multivariate linear regression analysis showed the two groups differed in portal venous pressure changes. The incidence of graft function and insulin independence was not different between the two groups. The SN and LH enzymes are associated with similar outcomes for IAT. Further optimization of the collagenase/neutral protease ratio is necessary to reduce the number of embedded islets obtained when using the SN enzyme. [source] Autologous transplantation in relapsed and refractory Hodgkin's diseaseEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2005Andreas Josting Abstract:, The current data support the use of high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) as standard procedure for the majority of patients with Hodgkin's disease (HD) relapsing or progressing after combination chemotherapy. Prognostic factors reflecting unfavourable prognostic features of the disease as well as resistance to conventional salvage therapy have been identified. Preliminary data suggests a high efficacy of high-dose sequential chemotherapies in these patients. An ongoing randomized trial is comparing standard HDCT versus sequential HDCT in patients with relapsed HD. [source] G-CSF-mobilized peripheral blood mononuclear cells from diabetic patients augment neovascularization in ischemic limbs but with impaired capabilityJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 5 2006B. ZHOU Summary.,Background: Autologous transplantation of mobilized peripheral blood mononuclear cells (M-PBMNCs) is a novel approach to improve critical limb ischemia (CLI) in diabetes. However, endothelial progenitor cells (EPCs) from diabetes are dysfunctional and impaired in ischemia-induced neovascularization. Objective: This study aimed to confirm the compromised efficiency of diabetic M-PBMNCs in therapeutic neovascularization, and to determine the underlying mechanisms of this impairment. Methods: Diabetic M-PBMNCs from 17 diabetic patients or healthy controls, or phosphate-buffered saline (PBS) were injected into the ischemic limbs of streptozotocin-induced diabetic nude mice. The limb blood perfusion, ambulatory score, ischemia damage, capillary/fiber ratio, arteriole density, collateral vessel formation, and pericytes recruitment were evaluated between these three groups. Non-invasive real time image and histopathology were used to detect the in vivo role of transplanted M-PBMNCs. Proliferation and adhesion of EPCs were assayed. In vitro vascular network incorporation and matrigel plug assay were used to test the pro-neovascularization role of M-PBMNCs. Results: Transplantation of diabetic M-PBMNCs also improved neovascularization, but to a lesser extent from that observed with non-diabetic ones. This was associated with the impairment of diabetic M-PBMNCs capacity to differentiate into EPCs, to incorporate into vessel-like tubules in vitro, to participate in vascular-like structure formation in a subcutaneous matrigel plug, and to stimulate the recruitment of pericytes/smooth muscle cells. In addition, there was impairment in vasculogenesis, which was related to the reduced adhesion ability of EPCs from diabetic M-PBMNCs. Conclusions: Diabetes reduced the capacity of M-PBMNCs to augment neovascularization in ischemia. [source] Calponin is expressed by fibroblasts and meningeal cells but not olfactory ensheathing cells in the adult peripheral olfactory systemGLIA, Issue 2 2007Chrystelle Ibanez Abstract Olfactory ensheathing cells (OECs), the principal glial cells of the peripheral olfactory system, have many phenotypic similarities with Schwann cells of the peripheral nervous system. This makes reliably distinguishing these two cells types difficult, especially following transplantation into areas of injury in the central nervous system. In an attempt to identify markers by which these two cells types can be distinguished, a recent proteomic analysis of fetal OECs and adult Schwann cells identified the actin-binding protein calponin as a potential marker expressed by OECs but not Schwann cells. Since many studies designed with the translational goal of autologous transplantation in mind have used adult OECs, this study examined the expression of calponin by adult OECs, both in vivo within the peripheral olfactory system and in vitro. Calponin colocalized with strongly fibronectin positive fibroblasts in the olfactory mucosa (OM) and meningeal cells in the olfactory bulb (OB) but not with S100, or neuropeptide-Y positive OECs. In tissue culture, calponin was strongly expressed by fibronectin-expressing fibroblasts from OM, sciatic nerve and skin and by meningeal cells from the OB, but not by p75NTR - and S100,-expressing OECs. These data, supported by Western blotting, indicate that calponin can not be used to distinguish adult OECs and Schwann cells. © 2006 Wiley-Liss, Inc. [source] Taking stem cells to the clinic: Major challengesJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2008Ariff Bongso Abstract Stem cell therapy offers tremendous promise in the treatment of many incurable diseases. A variety of stem cell types are being studied but human embryonic stem cells (hESCs) appear to be the most versatile as they are pluripotent and can theoretically differentiate into all the tissues of the human body via the three primordial germ layers and the male and female germ lines. Currently, hESCs have been successfully converted in vitro into functional insulin secreting islets, cardiomyocytes, and neuronal cells and transfer of such cells into diabetic, ischaemic, and parkinsonian animal models respectively have shown successful engraftment. However, hESC-derived tissue application in the human is fraught with the problems of ethics, immunorejection, tumorigenesis from rogue undifferentiated hESCs, and inadequate cell numbers because of long population doubling times in hESCs. Human mesenchymal stem cells (hMSC) though not tumorigenic, also have their limitations of multipotency, immunorejection, and are currently confined to autologous transplantation with the genuine benefits in allogeneic settings not conclusively shown in large controlled human trials. Human Wharton's jelly stem cells (WJSC) from the umbilical cord matrix which are of epiblast origin and containing both hESC and hMSC markers appear to be less troublesome in not being an ethically controversial source, widely multipotent, not tumorigenic, maintain "stemness" for several serial passages and because of short population doubling time can be scaled up in large numbers. This report describes in detail the hurdles all these stem cell types have to overcome before stem cell-based therapy becomes a genuine reality. J. Cell. Biochem. 105: 1352,1360, 2008. © 2008 Wiley-Liss, Inc. [source] Non-myeloablative conditioning and allogeneic transplantation for multiple myeloma,AMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2010Keren Osman In multiple myeloma (MM), allogeneic stem cell transplantation (alloHCT) carries a lower relapse risk than autologous transplantation but a greater transplant-related mortality. Nonmyeloablative conditioning for allogeneic transplantation (NST) reduces transplant-related toxicity. Results are encouraging when used during first remission in low-risk patients, but less-so in relapsed or refractory disease. This is a single-center retrospective analysis of 20 previously treated MM patients who underwent NST from matched-related or matched-unrelated donors from 2000,2006. Median age was 52.7 years (37.2,68.0). Twenty-five percent had advanced or high-risk disease. Eleven still had active disease prior to NST. Conditioning was total body irradiation 200 cGy on a single fraction on day ,5, followed by antithymocyte globulin (ATG) 1.5 mg/kg/day and fludarabine 30 mg/m2/day on days ,4 to ,2. All received immunosuppression, most commonly with oral mycofenylate mofetil and cyclosporine beginning on day ,5. At day 100, 50% had achieved complete remission. Transplant-related mortality was 25%. Median overall survival (OS) was 21.2 months (0.6,90+) and progression-free survival (PFS) 6.6 months (0.6,90+). Both OS and PFS were 24% at 3 years. OS was significantly greater for patients with age <52 years (median 27 months vs. 7.9 months, P = 0.031), and there was a trend toward greater OS for those with ,2 microglobulin <2.5 mg/l (median 27 months vs. 7.7 months, P = 0.08). Donor characteristics and Ig type had no significant effect on survival. These data suggest a benefit of NST in relapsed/refractory MM. Randomized trials must be performed to confirm and further qualify this benefit. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source] Idiotype-pulsed antigen presenting cells following autologous transplantation for multiple myeloma may be associated with prolonged survival,AMERICAN JOURNAL OF HEMATOLOGY, Issue 12 2009Martha Q. Lacy Vaccines are attractive as consolidation therapy after autologous stem cell transplantation (ASCT) for multiple myeloma (MM). We report the results of a phase II trial of the immunotherapeutic, APC8020 (MylovengeÔ), given after ASCT for MM. We compared the results with that of other patients with MM who underwent ASCT at Mayo Clinic during the same time period. Twenty-seven patients were enrolled on the trial between July, 1998 and June, 2001, and the outcomes were compared to that of 124 consecutive patients transplanted during the same period, but not enrolled on the trial. The median (range) follow-up for patients still alive from the vaccine trial is 6.5 (2.9,8 years), and 7.1 (6,8 years) in the control group. The median age was 57.4 range (36.1,71.3) in the DB group and 56.4 (range, 30,69) in the trial group. Known prognostic factors including PCLI, B2M, and CRP were comparable between the groups. The median overall survival for the trial patients was 5.3 years (95% CI: 4.0 years,N/A) compared to 3.4 years (95% CI: 2.7,4.6 years) for the DB group (P = 0.02). The median time to progression and progression-free survival for the trial group was similar to the DB group. Although not a controlled trial, the vaccines given after ASCT appear to be associated with improved overall survival compared to historical controls. This approach warrants further investigation to confirm this and define the role of vaccine therapy in myeloma. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc. [source] Factors predicting success or failure associated with common types of transplantsPEDIATRIC TRANSPLANTATION, Issue 2005Brian J. Bolwell Abstract:, The ability to predict clinical outcomes is essential to accurate medical decision analysis. Many accepted bone marrow transplant related prognostic variables are derived from data that is over 20-years old and may or may not be applicable to current medical practice. This report reviews both older data concerning bone marrow transplantation prognostic factors as well as more current reports. In addition to pretransplant variables, this review examines easily measured post-transplant variables that may affect prognosis, as well as data concerning the cellular component of the infused graft in both allogeneic and autologous transplantation. [source] Eradication of Multiple Myeloma and Breast Cancer Cells by TH9402-mediated Photodynamic Therapy: Implication for Clinical Ex Vivo Purging of Autologous Stem Cell Transplants,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 6 2000N. Brasseur ABSTRACT High-dose chemotherapy combined with autologous transplantation using bone marrow or peripheral blood-derived stem cells (PBSC) is now widely used in the treatment of hematologic malignancies as well as some solid tumors like breast cancer (BC). However, some controversial results were recently obtained in the latter case. The presence of malignant cells in the autograft has been associated with the recurrence of the disease, and purging procedures are needed to eliminate this risk. The aim of this study was to evaluate the potential of the photosensitizer 4,5-dibromorhodamine methyl ester (TH9402), a dibrominated rhodamine derivative, to eradicate multiple myeloma (MM) and BC cell lines, while sparing more than 50% of normal pluripotential blood stem cells from healthy volunteers. The human BC MCF-7 and T-47D and MM RPMI 8226 and NCI-H929 cell lines were used to optimize the photodynamic purging process. Cell concentration and the cell suspension thickness as well as the dye and light doses were varied in order to eventually treat 1,2 L of apheresis. The light source consisted of two fluorescent scanning tubes emitting green light centered about 515 nm. The cellular uptake of TH9402 was measured during the incubation and washout periods and after photodynamic treatment (PDT) using spectrofluorometric analysis. The limiting dilution assay showed that an eradication rate of more than 5 logs is obtained when using a 40 min incubation with 5,10 ,M dye followed by a 90 min washout period and a light dose of 5,10 J/cm2 (2.8 mW/cm2) in all cell lines. Agitating the 2 cm thick cell suspension containing 20 × 106 cells/mL during PDT was essential for maximal photoinactivation. Experiments on mobilized PBSC obtained from healthy volunteers showed that even more drastic purging conditions than those found optimal for maximal eradication of the malignant cell lines were compatible with a good recovery of hematopoietic progenitors cells. The absence of significant toxicity towards normal hematopoietic stem cells, combined with the 5 logs eradication of cancer cell lines induced by this procedure suggests that TH9402 offers an excellent potential as an ex vivo photodynamic purging agent for autologous transplantation in MM and BC treatment. [source] Insulin-Producing Cells Derived from Rat Bone Marrow and Their Autologous Transplantation in the Duodenal Wall for Treating DiabetesTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 5 2009Yu-Hua Zhang Abstract Islet cell transplantation is one of the most promising therapies for diabetes mellitus (DM). However, the limited availability of purified islets for transplantation and the risk of immunological rejection severely limit its use. In vitro transdifferentiation of autologous bone marrow-derived mesenchymal stem cells (BMSCs) into insulin-producing cells (IPCs) could provide an abundant source of cells for this procedure and avoid immunological rejection. Here, we isolated and characterized BMSCs and induced their in vitro differentiation into IPCs. Reverse-transcription polymerase chain reaction analysis revealed that these IPCs could express Ins1, Ins2, glucagon, glucose transporter 2, and pancreatic duodenal homeobox-1. Insulin production by the IPCs was confirmed by immunocytochemistry and Western blot analysis. On this basis, donor rats supplying BMSCs were made diabetic by a single intraperitoneal injection of streptozotocin. The IPCs were then autologously transplanted into the duodenal submucosa of diabetic rats. Grafted cells could be visualized in sections after 2, 4, and 8 weeks by immunohistochemical staining for insulin. Furthermore, in the IPC-implanted group, hyperglycemia was normalized, compared with a persistent increase in glucose levels in the diabetic group and intraperitoneal glucose tolerance test-induced responses were observed in the IPC-implanted group. These results on autologous transplantation of IPCs derived from BMSCs into the duodenal wall could offer a novel potential therapeutical protocol for DM. Anat Rec, 292:728,735, 2009. © 2009 Wiley-Liss, Inc. [source] Long-Term Result of the New Endoscopic Vocal Fold Medialization Surgical Technique for Laryngeal Palsy,THE LARYNGOSCOPE, Issue 2 2006Koichiro Nishiyama MD Abstract Objective: The conventional surgical method for a case of unilateral laryngeal nerve paralysis with large glottal gap requires an external cervical incision. In the present study, we developed an endoscopic technique of vocal fold medialization that can make the external incision unnecessary. This procedure of autologous transplantation of fascia into the vocal fold (ATFV) was developed for the successful treatment of unilateral laryngeal nerve paralysis. However, the method seemed to be effective only for patients with a relatively mild glottal gap. Study Design and Methods: In the present study, we modified the method of medialization using the ATFV technique to obtain effective closure of a large glottal gap. To overcome this difficulty, an attempt was made to extend the site of transplantation more posteriorly so as to adduct the vocal process of the arytenoid cartilage in the body of the vocal fold. Results: This new technique was applied to eight cases of patients with unilateral laryngeal paralysis with severe dysphonia. None of the patients showed any evidence of falling off of the graft. Elongation of the maximum phonation time and a decrease in airflow rate during phonation were obtained with improvement in voice quality in all patients 1 year after the surgery. Conclusions: This method, with its less invasive approach, proved to be useful for the treatment of large glottal gap due to unilateral laryngeal nerve paralysis. [source] Autologous Transplantation of Fascia into the Vocal Fold: Long-Term Result of Type-1 Transplantation and the Future,THE LARYNGOSCOPE, Issue S108 2005Koichi Tsunoda MD Abstract Objectives: Since 1997, we have performed the autologous transplantation of fascia into the vocal fold (ATFV) procedure on cases of sulcus vocalis. In what follows, we report the long-term results of our new surgical approach and discuss the role of these transplantations. We also review and report some complications that can be caused by ATFV. Finally, we discuss the ATFV technique as a contribution to the phonosurgery of the future. Study Design: Prospective study. Methods: We were able to obtain long-term results from 10 volunteer cases (2 female and 8 male, age: 15,71, mean 46.5 years old) who could be followed up for at least 3 years after transplantation. All were cases of pathologic sulcus vocalis. We measured maximum phonation time (MPT) and carried out pre- and postsurgical clinical observation and laryngeal stroboscopy in all cases. These measurements and observations were made before the ATFV and at 6 months, 1 year, 2 years, and 3 years after surgery. Results: In stroboscopic observation 1 year after the ATFV, satisfactory glottal closure and excellent mucosal wave were observed for all cases, and there was no case with hyperadduction of the false vocal folds. MPT measures remained at an improved level 2 years and 3 years after the transplantations. Paired-sample t tests showed that the improvement relative to preATFV levels was significant for all postsurgical measurements up to 3 years. Conclusions: We conclude that ATFV is a successful surgical procedure for sulcus vocalis and scarred vocal folds. Other phonosurgical clinical applications may also be envisioned. [source] Multiple myeloma: chemotherapy or transplantation in the era of new drugsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2010Antonio Palumbo Abstract Objective:,To review the current results of studies incorporating novel agents in multiple myeloma (MM) and discuss the role of autologous stem-cell transplantation (ASCT) in the era of new active drugs for the treatment of this disease. The outlook for patients with symptomatic MM is changing with the introduction of bortezomib, thalidomide, and lenalidomide into the repertoire of available chemotherapeutic agents. Compared with standard chemotherapy, a survival benefit has been reported for the first time in 30 yrs. Methods: Articles published in English between 1969 and 2008 were identified by searching PubMed for ,myeloma', ,diagnosis', ,thalidomide', ,bortezomib', ,lenalidomide', ,dexamethasone', ,prednisone', ,doxorubicin', ,cyclophosphamide', ,melphalan', ,combination chemotherapy', and ,autologous transplantation'. Results: In randomized studies, bortezomib, thalidomide, and lenalidomide have each been combined with dexamethasone, alkylating agents, or doxorubicin, and such combinations resulted in significant improvement in progression-free survival. Conclusions: The incorporation of new drugs as induction therapy along with ASCT appears to produce very good partial response rates, slightly superior to those achieved by conventional chemotherapy with new drugs. How to best optimize induction, consolidation, and maintenance therapy and how to best select and prepare patients for ASCT are still to be determined. Randomized trials are needed to directly compare the current best chemotherapeutic approach with best ASCT strategies and to guide clinical practice for patients with MM. [source] | |||||||||||||||||||||||||