A roundtable on responsible innovation with autologous stem cells in Australia, Japan and Singapore.

We report on a roundtable event hosted in Singapore that sought to identify some of the ethical and regulatory challenges in translating autologous cell-based interventions, particularly those claiming to involve stem cells, into safe and effective therapies and to propose some solutions to encourage responsible innovation with these products. Challenges are identified in the three areas of cell manufacturing and processing, innovative uses of autologous cells in clinical practice and standards of evidence. Proposed solutions are discussed within a co-operative model of statutory laws and regulations that can enable product development with autologous cells and professional codes and standards that can encourage ethical conduct in clinical practice. Future research should be directed toward establishing regional networks for the development of internationally consistent standards in manufacturing and ethical codes of conduct for innovating with stem cells, and other autologous cells, and fostering ongoing exchange between jurisdictions.

Immunologic Autograft Engineering and Survival in Non-Hodgkin Lymphoma.

Retrospective studies have reported that the collected and infused autograft absolute lymphocyte count (A-ALC) affects clinical outcomes after autologous peripheral hematopoietic stem cell transplantation (APHSCT). We hypothesized that manipulation of the apheresis machine to target a higher A-ALC dose would translate into prolonged progression-free survival (PFS) in patients with non-Hodgkin lymphoma (NHL) undergoing APHSCT. Between December 2007 and October 2010, we performed a double-blind, phase III, randomized study randomly assigning 122 patients with NHL to undergo collection with the Fenwal Amicus Apheresis system with our standard settings (mononuclear cells offset of 1.5 and RBC offset of 5.0) or at modified settings (mononuclear cells offset of 1.5 and RBC of 6.0). The primary endpoint was PFS. Neither PFS (hazard ratio [HR] of modified to standard, 1.13; 95% confidence interval [CI], .62 to 2.08; P = .70) nor overall survival (OS) (HR modified to standard, .85; 95% CI, .39 to 1.86; P = .68) were found to differ by collection method. Collection of A-ALC between both methods was similar. Both PFS (P = .0025; HR, 2.77; 95% CI, 1.39 to 5.52) and OS (P = .004; HR, 3.38; 95% CI, 1.27 to 9.01) were inferior in patients infused with an A-ALC < .5 × 10(9) lymphocytes/kg compared with patients infused with an A-ALC ≥ .5 × 10(9) lymphocytes/kg, regardless of the method of collection. We did not detect significant differences in clinical outcomes or in the A-ALC collection between the modified and the standard Fenwal Amicus settings; however, despite physician discretion on primary number of collections and range of cells infused, higher A-ALC infused dose were associated with better survival after APHSCT.

Ex vivo virotherapy with myxoma virus does not impair hematopoietic stem and progenitor cells.

BACKGROUND: Relapsing disease is a major challenge after hematopoietic cell transplantation for hematological malignancies. Myxoma virus (MYXV) is an oncolytic virus that can target and eliminate contaminating cancer cells from auto-transplant grafts. The aims of this study were to examine the impact of MYXV on normal hematopoietic stem and progenitor cells and define the optimal treatment conditions for ex vivo virotherapy. METHODS: Bone marrow (BM) and mobilized peripheral blood stem cells (mPBSCs) from patients with hematologic malignancies were treated with MYXV at various time, temperature and incubation media conditions. Treated BM cells from healthy normal donors were evaluated using flow cytometry for MYXV infection, long-term culture-initiating cell (LTC-IC) assay and colony-forming cell (CFC) assay. RESULTS: MYXV initiated infection in up to 45% of antigen-presenting monocytes, B cells and natural killer cells; however, these infections were uniformly aborted in >95% of all cells. Fresh graft sources showed higher levels of MYXV infection initiation than cryopreserved specimens, but in all cases less than 10% of CD34(+) cells could be infected after ex vivo MYXV treatment. MYXV did not impair LTC-IC colony numbers compared with mock treatment. CFC colony types and numbers were also not impaired by MYXV treatment. MYXV incubation time, temperature or culture media did not significantly change the percentage of infected cells, LTC-IC colony formation or CFC colony formation. CONCLUSIONS: Human hematopoietic cells are non-permissive for MYXV. Human hematopoietic stem and progenitor cells were not infected and thus unaffected by MYXV ex vivo treatment.

[Indices of intraoperative flowmetry, determining patency of grafts in the remote period after revascularization of the right coronary artery].

The authors studied the threshold values of ultrasound flowmetry concerning composite T-grafts, combined I-grafts, and autovenous shunts during revascularization of the right coronary artery (RCA), determining high risk for the development of shunt occlusion in the remote postoperative period. The retrospective study included a total of 223 patients subjected to revascularization of the RCA's basin with the help of composite T-grafts, combined I-grafts, and autovenous shunts. Depending on the method of bypass grafting of the RCA and its branches, all patients were subdivided into 3 groups: Group 1 was composed of 65 patients in whom the RCA basin was revascularized by a branch of the composite T-graft, Group 2 comprised 112 patients who endured autovenous aortocoronary bypass grafting, and Group 3 consisted of 46 patients in whom the RCA basin was shunted by a combined mammarovenous I-graft. The groups had no statistically significant differences on the main clinical and demographic parameters. Intraoperative assessment of the blood flow through the coronary shunts was carried out by means of ultrasound flowmetry. The remote results were evaluated based on the findings of the control coronaroshuntography which was carried out in all patients within the terms varying from 16 to 43 months. In the remote period in Group 1 patients (T-graft), 59 (90%) mammary shunts were patent, in Group 2 - 99 (88.4%) autovenous shunts, and in Group 3 (I-graft) 42 (95.5%) shunt were patent. Cumulative probability of freedom from shunt occlusion within the terms up to 3 years after surgery in Group 1 amounted to 82±0.5%, in Group 2 to 58±2.1%, and in Group 3 to 86±1.9%, with the differences between Group 2 and other groups being statistically significant (p=0.01). The Poisson regression analysis showed that the risk for graft occlusion increased by 10% with the resistance index in the branch of the T-graft from 4.0; by 8% with the resistance index in the autovein from 2.9; and by 3% with the index of resistance in the I-graft from 3.2. The conclusion was made that composite T-grafts and combined I-grafts demonstrated similar results of patency within the terms up to 3 years, possessing advantages over autovenous conduits while shunting the RCA basin. The optimal index of peripheral resistance for the autovein during revascularization of the RCA basin is up to 2.9; for the combined T-graft - up to 3.2, and for the composite T-graft - up to 4.0. Probability of shunt occlusion in the remote period does not depend upon the average volumetric blood velocity (Qmean) but is directly proportional to the value of the pulsatility index (Pi) which reflects the state of the distal bed.

Load Sharing and Endplate Pressure Distribution in Anterior Interbody Fusion Influenced by Graft Choice.

BACKGROUND: Cage subsidence is a known complication of spinal fusion. Various aspects of cage design have been investigated for their influence on cage subsidence, whereas the potential contribution of graft material to load sharing is often overlooked. We aimed to determine whether graft in the aperture affects endplate pressure distribution. METHODS: The pressure distributions of a polyetheretherketone interbody cage with 3 different aperture graft conditions were evaluated: empty, demineralized bone matrix, and supercritical CO2-treated allograft bone crunch (SCCO2). RESULTS: Graft materials contributed as much as half the load transmission for SCCO2, whereas demineralized bone matrix contributed one third. Endplate areas in contact with the cage demonstrated decreased areas within the highest-pressure spectrum with SCCO2 graft materials compared with empty cages. CONCLUSIONS: Graft choice plays a role in reducing peak endplate pressures. This finding is relevant to implant subsidence, as well as graft loading and remodeling.

A Novel Embolization Technique for Renal Hemorrhage Complication by Autologous Fat Tissue

The percutaneous nephrolithotomy method is the most used treatment option for urinary stone disease. Bleeding is the most feared complication of this method. Transcatheter coil or medical glue embolization is currently the used treatment option for this bleeding complication. The aim of this report to show the novel subcutaneous fat tissue embolization technique for percutaneous nephrolithotomy related bleeding complications. In these two cases, we treated the percutaneous nephrolithotomy related bleeding complication with subcutaneous fat tissue. Subcutaneous fat tissue was taken with subcutaneous fascia from the femoral site by 1 cm incision. This tissue to be used for embolization was passed on the 0.014 guidewire from the back end of this guidewire (like shish kebab). The fat tissue passed on the 0.014 wire was sent to the bleeding site through the guiding catheter and guideliner, over the 0.014 guidewire with the monorail balloon (as a pusher) placed behind this fat tissue. The subcutaneous fat tissue with subcutaneous fascia embolization was completely stopped the bleeding and fistula. We have successfully used a novel embolization technique for fat tissue embolization to the bleeding site (Ari technique). Subcutaneous fat tissue embolization with the novel embolization technique for percutaneous nephrolithotomy related bleeding is a safe and reliable treatment option.

Creation of the bone bank of the Rabat and Casablanca region in Morocco.

For a long time the use of bone grafting has demonstrated its interest in orthopedic surgery and traumatology. The autografts which are still very frequently used present various problems. On the one hand, it is necessary to find a correct mechanical quality and a sufficient quantity of bone. On the other hand, the graft removal lengthens the operative time and generally painful in postoperative. These disadvantages of autografts have led to the development of bone allografts. Indeed, the low immunogenic power of the bone, the good integration of the graft and the ease of bone preservation techniques make it possible to overcome the various problems posed by bone autografts. The increasing use of bone allografts has resulted in the need for a structure allowing the management of graft stocks. The purpose of this work is to demonstrate the mode of operation of a bone bank, whose conservation activity is limited to the femoral heads treated by cryopreservation and without secondary sterilization process. The bank collaborates with all orthopedic surgeons in the Rabat and Casablanca city at first and then with all orthopedic surgeons in Morocco. It provides allografts in quality and safety.

Back to Basics: Autologous Tissue: 1.5 www.aornjournal.org/content/cme.

Perioperative personnel manage autologous tissue when they care for patients undergoing procedures requiring the use of bone, soft tissue, or other autologous tissue to repair or replace defects. Use of autologous tissue can minimize the risk of rejection, disease transfer, and infection compared with the use of artificial materials. There are important steps to follow when handling autologous tissue to ensure it is safe for replantation and does not become contaminated. This Back to Basics article provides strategies for managing some types of autologous tissue, including bone flaps, parathyroid tissue, skin grafts, and veins. Tissue management strategies include creating strict documentation policies, standardizing processes and communication, and implementing routine audits to assess compliance.