Post‐thaw viable CD34<sup>+</sup> cell count is a valuable predictor of haematopoietic stem cell engraftment in autologous peripheral blood stem cell transplantation

Lee, Sang-Guk; Kim, S.; Kim, H.; Baek, Eun Jung; Jin, Hyungyu; Kim, J.

doi:10.1111/j.1423-0410.2007.01009.x

Cited by 57 publications

(60 citation statements)

References 18 publications

(21 reference statements)

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“…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). Indeed, many studies have suggested that DMSO depletion can reduce adverse reactions, with minimum effects or even improvements on engraftment after HSC transplantation (2,5,7,13,55,105,106). Given the lack of consensus, no specific requirements regarding removal of DMSO from HSC grafts prior to infusion have been issued by the regulatory agencies or accreditation associations, instead leaving the decision to the discretion of physicians and clinical institutions to set their own policies and guidelines.…”

Section: Physiological Role Of Dmso In Adverse Reactionsmentioning

confidence: 99%

“…Many approaches have been applied to reduce the adverse effects of cryopreserved hematopoietic stem cell transplantation, such as: (1) systematic premedication before infusion (62), (2) hydration and allopurinol administration after infusion (62); (3) slowing down the infusion speed and prolonging the infusion time (2,62), (4) dividing the infusion into multiple aliquots given several hours or days apart (10,62); (5) further concentrating HSC grafts to reduce the cryopreservation volumes and corresponding DMSO content (2); (6) reducing % DMSO concentration for cryopreservation to lower than 10%, or use alternative CPA to mix with or replace DMSO (2,108–110); and (7) removing DMSO before infusion (2,5,7,13,55,105,106). Since the side effects are idiosyncratic thus unpredictable so far to our knowledge, all these approaches are suggested to be combined to reduce the reaction incidence as low as possible.…”

Section: Reducing the Infusional Side Effects Of Cryopreserved Hsc Grmentioning

confidence: 99%

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

Shu

Heimfeld

Gao

2013

Bone Marrow Transplant

184

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%

Section: Reducing the Infusional Side Effects Of Cryopreserved Hsc Grmentioning

confidence: 99%

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

Shu

Heimfeld

Gao

2013

Bone Marrow Transplant

184

182

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“…In some sensitive cell cultures, such as of embryonic stem cells, the presence of necrotic cells release factors that negatively impact the health of the entire culture in a cascading manner 2, 5 , therefore periodic removal of dead cells improves culture health. Also the presence of nonviable cells can be detrimental to clinical outcomes of cell therapies, for example the delaying of engraftment time of hematopoietic stem cell transplantation 6–8 . While the immune system of organisms can identify and remove dead and dying cells from the body, the presence of debris and dead cells in in vitro cell culture adversely affects its quality and productivity.…”

Section: Introductionmentioning

confidence: 99%

Microfluidic Sorting of Cells by Viability Based on Differences in Cell Stiffness

Islam

Brink

Blanche

et al. 2017

Sci Rep

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The enrichment of viable cells is an essential step to obtain effective products for cell therapy. While procedures exist to characterize the viability of cells, most methods to exclude nonviable cells require the use of density gradient centrifugation or antibody-based cell sorting with molecular labels of cell viability. We report a label-free microfluidic technique to separate live and dead cells that exploits differences in cellular stiffness. The device uses a channel with repeated ridges that are diagonal with respect to the direction of cell flow. Stiff nonviable cells directed through the channel are compressed and translated orthogonally to the channel length, while soft live cells follow hydrodynamic flow. As a proof of concept, Jurkat cells are enriched to high purity of viable cells by a factor of 185-fold. Cell stiffness was validated as a sorting parameter as nonviable cells were substantially stiffer than live cells. To highlight the utility for hematopoietic stem cell transplantation, frozen samples of cord blood were thawed and the purity of viable nucleated cells was increased from 65% to over 94% with a recovery of 73% of the viable cells. Thus, the microfluidic stiffness sorting can simply and efficiently obtain highly pure populations of viable cells.

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“…Before freezing, the total number of CD34+ cells is determined, and this number is used post-thaw to determine the total cell number administered to the patient. In a 2008 study by Lee et al [87], PBSCs were analyzed via flow cytometry of 7-AAD and CD34 after collection from 36 patients and immediately post-thaw. Thawed PBSCs were administered to patients and the time to engraftment was determined by daily blood counts.…”

Section: Preclinical Assays For Qualitymentioning

confidence: 99%

Cryopreservation of Hematopoietic Stem Cells: Emerging Assays, Cryoprotectant Agents, and Technology to Improve Outcomes

Hornberger

McKenna

et al. 2019

Transfus Med Hemother

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Hematopoietic stem cell (HSC) therapy is widely used to treat a growing number of hematological and non-hematological diseases. Cryopreservation of HSCs allows for cells to be transported from the site of processing to the site of clinical use, creates a larger window of time in which cells can be administered to patients, and allows sufficient time for quality control and regulatory testing. Currently, HSCs and other cell therapies conform to the same cryopreservation techniques as cells used for research purposes: cells are cryopreserved in dimethyl sulfoxide (DMSO) at a slow cooling rate. As a result, HSC therapy can result in numerous adverse symptoms in patients due to the infusion of DMSO. Efforts are being made to improve the cryopreservation of HSCs for clinical use. This review discusses advances in the cryopreservation of HSCs from 2007 to the present. The preclinical development of new cryoprotectants and new technology to eliminate cryoprotectants after thawing are discussed in detail. Additional cryopreservation considerations are included, such as cooling rate, storage temperature, and cell concentration. Preclinical cell assessment and quality control are discussed, as well as clinical studies from the past decade that focus on new cryopreservation protocols to improve patient outcomes.

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Post‐thaw viable CD34⁺ cell count is a valuable predictor of haematopoietic stem cell engraftment in autologous peripheral blood stem cell transplantation

Cited by 57 publications

References 18 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

Microfluidic Sorting of Cells by Viability Based on Differences in Cell Stiffness

Cryopreservation of Hematopoietic Stem Cells: Emerging Assays, Cryoprotectant Agents, and Technology to Improve Outcomes

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Post‐thaw viable CD34+ cell count is a valuable predictor of haematopoietic stem cell engraftment in autologous peripheral blood stem cell transplantation

Cited by 57 publications

References 18 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

Microfluidic Sorting of Cells by Viability Based on Differences in Cell Stiffness

Cryopreservation of Hematopoietic Stem Cells: Emerging Assays, Cryoprotectant Agents, and Technology to Improve Outcomes

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Post‐thaw viable CD34⁺ cell count is a valuable predictor of haematopoietic stem cell engraftment in autologous peripheral blood stem cell transplantation