Washing of cord blood grafts after thawing: high cell recovery using an automated and closed system*

Rodríguez, Laura; Azqueta, Carmen; Azzalin, S; Garcı́a, Juan Carlos; Querol, Sergi

doi:10.1111/j.1423-0410.2004.00550.x

Cited by 50 publications

(43 citation statements)

References 17 publications

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“…Cordoba et al found that, despite DMSO depletion and adequate histamine blockage, side effects continued to appear, suggested other factors such as number of granulocytes in the thawed product were more important than DMSO content, and perhaps removal of DMSO was not needed (4). However, most investigators believe removing DMSO before infusion is beneficial (2,3,5,8–11,13,15,18,20,36,52,56,59,62,64,69,73,74,104). In addition, most DMSO depletion strategies will also concomitantly remove cell debris and reduce neutrophil, platelet and other blood cell-derived soluble mediators, which may further contribute to decreasing the adverse event incidence and severity (2).…”

Section: Physiological Role Of Dmso In Adverse Reactionsmentioning

confidence: 99%

Hematopoietic SCT with cryopreserved grafts: adverse reactions after transplantation and cryoprotectant removal before infusion

Shu

Heimfeld

Gao

2013

Bone Marrow Transplant

190

182

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Transplantation of hematopoietic stem cells (HSC) has been successfully developed as a part of treatment protocols for a large number of clinical indications, and cryopreservation of both autologous and allogeneic sources of HSC grafts is increasingly being employed to facilitate logistical challenges in coordinating the collection, processing, preparation, quality control testing and release of the final HSC product with delivery to the patient. Direct infusion of cryopreserved cell products into patients has been associated with the development of adverse reactions, ranging from relatively mild symptoms to much more serious, life-threatening complications, including allergic/gastrointestinal/cardiovascular/neurological complications, renal/hepatic dysfunctions, etc. In many cases the cryoprotective agent (CPA) used — which is typically dimethyl sulfoxide (DMSO), is believed to be the main causal agent of these adverse reactions and thus many studies recommend depletion of DMSO before cell infusion. In this paper, we will briefly review the history of HSC cryopreservation, the side effects reported after transplantation, along with advances in strategies for reducing the adverse reactions, including methods and devices for removal of DMSO. Strategies to minimize adverse effects include medication before and after transplantation, optimizing the infusion procedure, reducing the DMSO concentration or using alternative CPAs for cryopreservation, and removing DMSO prior to infusion. For DMSO removal, besides the traditional and widely applied method of centrifugation, new approaches have been explored in the last decade, such as filtration by spinning membrane, stepwise dilution-centrifugation using rotating syringe, diffusion-based DMSO extraction in microfluidic channels, dialysis and dilution-filtration through hollow-fiber dialyzers, and some instruments (CytoMate™, Sepax S-100, Cobe 2991, microfluidic channels, dilution-filtration system, etc.) as well. However, challenges still remain: development of the optimal (fast, safe, simple, automated, controllable, effective, and low-cost) methods and devices for CPA removal with minimum cell loss and damage remains an unfilled need.

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Section: Physiological Role Of Dmso In Adverse Reactionsmentioning

confidence: 99%

Hematopoietic SCT with cryopreserved grafts: adverse reactions after transplantation and cryoprotectant removal before infusion

Shu

Heimfeld

Gao

2013

Bone Marrow Transplant

190

182

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“…Average CB TNC recoveries reported with Sepax volume reduction are in the range of 80-87% (mean ¼ 84.2) with CD34 recoveries being slightly higher 86%. Hematocrits are in the 36-45% range (data from Rodrı´guez et al 35 and Lapierre et al 36 and Sepax website). These results compare well with those achievable by manual techniques using Hespan to accelerate red cell settling and top-and-bottom bag centrifugation.…”

Section: Cbu Processing For Bankingmentioning

confidence: 99%

Cord blood banking for clinical transplantation

Rubinstein

2009

Bone Marrow Transplant

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Cord blood (CB) stem and progenitor cells from related donors have been transplanted for past 20 years and from unrelated donors issued by public CB banks for 16 years. This brief look at public CB banking highlights aspects of its current status to suggest that accomplishing the currently required tasks, though no small undertaking, is not enough: much remains to be contributed. CB banking started in the 1930s, collecting blood for transfusion and showed that CB could be effectively collected, stored and administered intravenously without negative consequences. The realization that it contains hematopoietic 'stem' cells (actually, colony-forming units) followed discoveries elsewhere in hematopoiesis research, while HLA and unrelated BMT were being investigated. Progress in the exploration of ethnically stratified HLA allele frequencies, together with plausible neonatal (partial) immunological tolerance, seemed to predict initially frequent, unavoidable, but sufficiently tolerable HLA mismatching with CB grafts. Gluckman et al. and Boyse et al. proved that HLA-identical sibling CB grafts led to definitive engraftment. Technical developments in processing and freezing enabled public banks to accumulate large inventories and to supply grafts that could succeed despite major HLA incompatibility and low cell doses and provide hope for universal access to unrelated-donor transplantation. Public CB banking has thrived worldwide. Regulation and accreditation defined Good Tissue Practice in the CB banking environment and provided accepted do's, don't's and how to's. Startling advances continue to be made, not only technical, but including the description of molecular regulation in the function of natural killer and other cells involved in allogeneic recognition that will have dramatic effects and will permit further improvement in CB selection and use.

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“…For the quantitative analysis of the Oil Red O and Fast-Red stained conachieved with a commercially available system (Sepax S-100, Biosafe, Switzerland) ( Fig. 1a), which is widely tent in the histological staining, a densitometric analysis was performed using the ImageJ software (National used for isolation of cord blood mononuclear cells prior to cryopreservation (27). We utilized a novel protocol Institute of Health, USA).…”

Section: Differentiation Studiesmentioning

confidence: 99%

Good Manufacturing Practice-Compliant Expansion of Marrow-Derived Stem and Progenitor Cells for Cell Therapy

et al. 2007

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Ex vivo expansion is being used to increase the number of stem and progenitor cells for autologous cell therapy. Initiation of pivotal clinical trials testing the efficacy of these cells for tissue repair has been hampered by the challenge of assuring safe and high-quality cell production. A strategy is described here for clinical-scale expansion of bone marrow (BM)-derived stem cells within a mixed cell population in a completely closed process from cell collection through postculture processing using sterile connectable devices. Human BM mononuclear cells (BMMNC) were isolated, cultured for 12 days, and washed postharvest using either standard open procedures in laminar flow hoods or using automated closed systems. Conditions for these studies were similar to long-term BM cultures in which hematopoietic and stromal components are cultured together. Expansion of marrow-derived stem and progenitor cells was then assessed. Cell yield, number of colony forming units (CFU), phenotype, stability, and multilineage differentiation capacity were compared from the single pass perfusion bioreactor and standard flask cultures. Purification of BMMNC using a closed Ficoll gradient process led to depletion of 98% erythrocytes and 87% granulocytes, compared to 100% and 70%, respectively, for manual processing. After closed system culture, mesenchymal progenitors, measured as CD105 + CD166 + CD14 − CD45 − and fibroblastic CFU, expanded 317-and 364-fold, respectively, while CD34 + hematopoietic progenitors were depleted 10-fold compared to starting BMMNC. Cultured cells exhibited multilineage differentiation by displaying adipogenic, osteogenic, and endothelial characteristics in vitro. No significant difference was observed between manual and bioreactor cultures. Automated culture and washing of the cell product resulted in 181 × 10 6 total cells that were viable and contained fibroblastic CFU for at least 24 h of storage. A combination of closed, automated technologies enabled production of good manufacturing practice (GMP)-compliant cell therapeutics, ready for use within a clinical setting, with minimal risk of microbial contamination.

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Washing of cord blood grafts after thawing: high cell recovery using an automated and closed system*

Cited by 50 publications

References 17 publications

Hematopoietic SCT with cryopreserved grafts: adverse reactions after transplantation and cryoprotectant removal before infusion

Hematopoietic SCT with cryopreserved grafts: adverse reactions after transplantation and cryoprotectant removal before infusion

Cord blood banking for clinical transplantation

Good Manufacturing Practice-Compliant Expansion of Marrow-Derived Stem and Progenitor Cells for Cell Therapy

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