How old is too old?

Colony-forming units assay Cryopreservation Hematopoietic stem cell transplantation Hematopoietic stem cells In vitro techniques Long-term storage Peripheral blood stem cell Transplant Viability

Journal

World journal of stem cells
ISSN: 1948-0210
Titre abrégé: World J Stem Cells
Pays: United States
ID NLM: 101535826

Informations de publication

Date de publication:
26 May 2020
Historique:
received: 28 02 2020
revised: 14 04 2020
accepted: 28 04 2020
entrez: 18 6 2020
pubmed: 18 6 2020
medline: 18 6 2020
Statut: ppublish

Résumé

Peripheral blood stem cells (PBSC) are commonly cryopreserved awaiting clinical use for hematopoietic stem cell transplant. Long term cryopreservation is commonly defined as five years or longer, and limited data exists regarding how long PBSC can be cryopreserved and retain the ability to successfully engraft. Clinical programs, stem cell banks, and regulatory and accrediting agencies interested in product stability would benefit from such data. Thus, we assessed recovery and colony forming ability of PBSC following long-term cryopreservation as well as their ability to engraft in NOD/SCID/IL-2Rγ To investigate the in vivo engraftment potential of long-term cryopreserved PBSC units. PBSC units which were collected and frozen using validated clinical protocols were obtained for research use from the Cellular Therapy Laboratory at Indiana University Health. These units were thawed in the Cellular Therapy Laboratory using clinical standards of practice, and the pre-freeze and post-thaw characteristics of the units were compared. Progenitor function was assessed using standard colony-forming assays. CD34-selected cells were transplanted into immunodeficient mice to assess stem cell function. Ten PBSC units with mean of 17 years in cryopreservation (range 13.6-18.3 years) demonstrated a mean total cell recovery of 88% ± 12% (range 68%-110%) and post-thaw viability of 69% ± 17% (range 34%-86%). BFU-E growth was shown in 9 of 10 units and CFU-GM growth in 7 of 10 units post-thaw. Immunodeficient mice were transplanted with CD34-selected cells from four randomly chosen PBSC units. All mice demonstrated long-term engraftment at 12 wk with mean 34% ± 24% human CD45+ cells, and differentiation with presence of human CD19+, CD3+ and CD33+ cells. Harvested bone marrow from all mice demonstrated growth of erythroid and myeloid colonies. We demonstrated engraftment of clinically-collected and thawed PBSC following cryopreservation up to 18 years in NSG mice, signifying likely successful clinical transplantation of PBSC following long-term cryopreservation.

Sections du résumé

BACKGROUND BACKGROUND
Peripheral blood stem cells (PBSC) are commonly cryopreserved awaiting clinical use for hematopoietic stem cell transplant. Long term cryopreservation is commonly defined as five years or longer, and limited data exists regarding how long PBSC can be cryopreserved and retain the ability to successfully engraft. Clinical programs, stem cell banks, and regulatory and accrediting agencies interested in product stability would benefit from such data. Thus, we assessed recovery and colony forming ability of PBSC following long-term cryopreservation as well as their ability to engraft in NOD/SCID/IL-2Rγ
AIM OBJECTIVE
To investigate the in vivo engraftment potential of long-term cryopreserved PBSC units.
METHODS METHODS
PBSC units which were collected and frozen using validated clinical protocols were obtained for research use from the Cellular Therapy Laboratory at Indiana University Health. These units were thawed in the Cellular Therapy Laboratory using clinical standards of practice, and the pre-freeze and post-thaw characteristics of the units were compared. Progenitor function was assessed using standard colony-forming assays. CD34-selected cells were transplanted into immunodeficient mice to assess stem cell function.
RESULTS RESULTS
Ten PBSC units with mean of 17 years in cryopreservation (range 13.6-18.3 years) demonstrated a mean total cell recovery of 88% ± 12% (range 68%-110%) and post-thaw viability of 69% ± 17% (range 34%-86%). BFU-E growth was shown in 9 of 10 units and CFU-GM growth in 7 of 10 units post-thaw. Immunodeficient mice were transplanted with CD34-selected cells from four randomly chosen PBSC units. All mice demonstrated long-term engraftment at 12 wk with mean 34% ± 24% human CD45+ cells, and differentiation with presence of human CD19+, CD3+ and CD33+ cells. Harvested bone marrow from all mice demonstrated growth of erythroid and myeloid colonies.
CONCLUSION CONCLUSIONS
We demonstrated engraftment of clinically-collected and thawed PBSC following cryopreservation up to 18 years in NSG mice, signifying likely successful clinical transplantation of PBSC following long-term cryopreservation.

Identifiants

pubmed: 32547684
doi: 10.4252/wjsc.v12.i5.359
pmc: PMC7280863
doi:

Types de publication

Journal Article

Langues

eng

Pagination

359-367

Informations de copyright

©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.

Déclaration de conflit d'intérêts

Conflict-of-interest statement: Goebel WS receives fees as a consulting medical director for Cook Regentec, LLC, and serves as medical director for Ossium Health, Inc. All other authors report no potential conflicts of interest.

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Auteurs

John Underwood (J)

Departments of Internal Medicine and Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, United States.

Mahvish Rahim (M)

Department of Pediatrics, Division of Pediatric Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN 46202, United States.

Carijo West (C)

Cellular Therapy Laboratory, Indiana University Health, Indianapolis, IN 46202, United States.

Rebecca Britton (R)

Cellular Therapy Laboratory, Indiana University Health, Indianapolis, IN 46202, United States.

Elaine Skipworth (E)

Cellular Therapy Laboratory, Indiana University Health, Indianapolis, IN 46202, United States.

Vicki Graves (V)

Cellular Therapy Laboratory, Indiana University Health, Indianapolis, IN 46202, United States.

Steven Sexton (S)

Cellular Therapy Laboratory, Indiana University Health, Indianapolis, IN 46202, United States.

Hillary Harris (H)

Cellular Therapy Laboratory, Indiana University Health, Indianapolis, IN 46202, United States.

Dave Schwering (D)

Cellular Therapy Laboratory, Indiana University Health, Indianapolis, IN 46202, United States.

Anthony Sinn (A)

Department of Pediatrics, Herman B Wells Center for Pediatric Research, In Vivo Therapeutics Core and Angio Biocore Shared Resource Facilities for the Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, United States.

Karen E Pollok (KE)

Department of Pediatrics, Division of Pediatric Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN 46202, United States.

Kent A Robertson (KA)

Department of Pediatrics, Division of Pediatric Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN 46202, United States.

W Scott Goebel (WS)

Department of Pediatrics, Division of Pediatric Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN 46202, United States. sgoebel2@iu.edu.

Kerry M Hege (KM)

Department of Pediatrics, Division of Pediatric Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN 46202, United States.

Classifications MeSH