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Kolle S.-F.T.,Copenhagen University | Fischer-Nielsen A.,Cell Therapy Facility | Mathiasen A.B.,Heart Center | Elberg J.J.,Copenhagen University | And 7 more authors.
The Lancet | Year: 2013

Background Autologous fat grafting is increasingly used in reconstructive surgery. However, resorption rates ranging from 25% to 80% have been reported. Therefore, methods to increase graft viability are needed. Here, we report the results of a triple-blind, placebo-controlled trial to compare the survival of fat grafts enriched with autologous adiposederived stem cells (ASCs) versus non-enriched fat grafts. Methods Healthy participants underwent two liposuctions taken 14 days apart: one for ASC isolation and ex-vivo expansion, and another for the preparation of fat grafts. Two purified fat grafts (30 mL each) taken from the second liposuction were prepared for each participant. One graft was enriched with ASCs (20 ×106 cells per mL fat), and another graft without ASC enrichment served as a control. The fat grafts were injected subcutaneously as a bolus to the posterior part of the right and left upper arm according to the randomisation sequence. The volumes of injected fat grafts were measured by MRI immediately after injection and after 121 days before surgical removal. The primary goal was to compare the residual graft volumes of ASC-enriched grafts with those of control grafts. This study is registered at www.clinicaltrialsregister.eu, number 2010-023006-12. Findings 13 participants were enrolled, three of whom were excluded. Compared with the control grafts, the ASCenriched fat grafts had significantly higher residual volumes: 23·00 (95% CI 20· 57-25· 43) cm3 versus 4· 66 (3· 16-6· 16) cm3 for the controls, corresponding to 80· 9% (76· 6-85· 2) versus 16· 3% (11· 1-21· 4) of the initial volumes, respectively (p<0· 0001). The difference between the groups was 18· 34 (95% CI 15· 70-20· 98) cm3, equivalent to 64· 6% (57· 1-72· 1; p<0· 0001). No serious adverse events were noted. Interpretation The procedure of ASC-enriched fat grafting had excellent feasibility and safety. These promising results add significantly to the prospect of stem cell use in clinical settings, and indicate that ASC graft enrichment could render lipofilling a reliable alternative to major tissue augmentation, such as breast surgery, with allogeneic material or major fl ap surgery.

Niam M.,Cell Therapy Facility | Linn Y.-C.,Singapore General Hospital | Fook Chong S.,Singapore General Hospital | Lim T.-J.,Cell Therapy Facility | And 6 more authors.
Experimental Hematology | Year: 2011

Objective: In our clinical studies involving cytokine-induced killer (CIK) cells for patients with hematological malignancies, starting cells came from a heterogeneous group of patients and donors. Here we study the feasibility of expansion and analyzed the characteristics of the end product from starting cells derived from different sources and at different disease states. Materials and Methods: Seventy-five clinical scale cultures were grown from 28 patients and 20 donors in Good Manufacturing Practices facilities under CIK condition. Results: CIK cells could be successfully expanded from healthy donors, patients with acute myeloid leukemia recovering from chemotherapy, untreated patients with acute myeloid leukemia or myelodysplastic syndrome with circulating leukemic blasts, and patients with chronic myeloid leukemia on imatinib. Furthermore, CIK cells of donor origin could be expanded from leukapheresis product collected from patients who relapsed post-allogeneic transplantation, thereby offering a useful method of obtaining activated donor cells in patients for whom further donor cells were unavailable. Interestingly, CIK cells cultured from patients with untreated acute myeloid leukemia and myelodysplastic syndrome had a significantly higher proportion of CD3 +CD56 + subset and higher fold expansion of CD3 + cells as compared to other groups of patients or healthy donors. Multivariate analysis showed that fresh starting cells expanded better than frozen-thawed cells, while prior exposure to granulocyte colony-stimulating factor or imatinib before harvesting did not adversely affect CIK cell expansion. Conclusions: Clinical scale expansion of CIK cells is feasible from both healthy donors and leukemia patients at various stages of treatment. This robust system allows clinical translation using CIK cells as immunotherapy in various clinical settings. © 2011 ISEH - Society for Hematology and Stem Cells.

Linn Y.-C.,Singapore General Hospital | Yong H.-X.,Singapore General Hospital | Niam M.,Cell Therapy Facility | Lim T.-J.,Cell Therapy Facility | And 10 more authors.
Cytotherapy | Year: 2012

Background aims. Cytokine-induced killer (CIK) cells have shown remarkable cytotoxicity against various tumors in vitro and in animal studies. We report on the clinical outcome of autologous CIK cells for patients with acute (AML) and chronic (CML) myeloid leukemia in remission. Methods. Eleven of the 13 recruited AML patients undergoing autologous peripheral blood stem cell transplant (autoPBSCT) were given autologous CIK cell infusion upon engraftment post-transplant and followed-up for disease relapse. Eleven CML patients on Imatinib with residual disease detectable by polymerase chain reaction (PCR) were given infusion and monitored by quantitation of the bcr-abl transcript. Results. Despite the presence of interferon (IFN)-γ-secreting T cells against various AML- and CML-associated peptides at sporadic time-points and demonstration of in vitro cytotoxicity of CIK cells against autologous and allogeneic AML targets, there was no survival benefit in AML patients post-autoPBSCT given CIK cells compared with historical controls. For CML patients, all continued to have a detectable bcr-abl transcript fluctuating within a range comparable to their pre-treatment baseline, although two had a transient but non-sustainable disappearance of bcr-abl transcript. There were no adverse reactions except for fever within the first day of infusion. Conclusions. Our small series, while confirming safety, failed to demonstrate a clinical benefit of autologous CIK cells given in its current form for AML and CML. Further manipulation of CIK cells to improve anti-leukemic potency and specificity, together with the preparation of patients to create a more conducive milieu for in vivo expansion and persistence of infused CIK cells, should be explored. © 2012 Informa Healthcare.

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