Phenotypic characterization and preclinical production of human lineage-negative cells for regenerative stem cell therapy - PubMed (original) (raw)
Phenotypic characterization and preclinical production of human lineage-negative cells for regenerative stem cell therapy
Dirk Strunk et al. Transfusion. 2005 Mar.
Abstract
Background: Regenerative stem cell therapy (SCT) is currently being tested in clinical trials. The ideal type and source of cells have not yet been defined. Lineage (Lin) depletion is an experimental procedure capable of enriching all recently recognized SC types with regenerative potency. This study was performed to define a practicable monoclonal antibody (MoAb) cocktail for Lin depletion and to test whether clinical-scale Lin depletion is possible.
Study design and methods: MoAbs (CD2/14/15/19/41/56/glycophorin A) were selected to mark seven mature hematopoietic lineages. Lin7-negative (Lin7NEG) cells were analyzed in peripheral blood (PB, n = 9), mobilized PB (MPB, n = 5), umbilical cord blood (UCB, n = 5), and marrow aspirates (BM, n = 4) by flow cytometry. Preclinical Lin depletion was tested with leukapheresis products from PB following good manufacturing practice (GMP) principles.
Results: Lin7NEG cells comprised 0.23 +/- 0.04, 0.27 +/- 0.03, 0.53 +/- 0.07, and 0.49 +/- 0.03 percent of PB, MPB, UCB, and BM, respectively. Basophils, CD34+, and dendritic cells constituted the major Lin7NEG subpopulations (84 +/- 2, 90 +/- 3, 40 +/- 3, and 80 +/- 3% in PB, MPB, UCB, and BM, respectively). Minor populations included CD7- and CD45- cells. Preclinical CD2/14/15/19/56 (Lin5) depletion after automated red blood cell and platelet reduction resulted in up to a 16.7-fold enrichment of CD34+ and CD34-/Lin5NEG cells.
Conclusions: A seven-MoAb cocktail is sufficient to label more than 99 percent of nucleated cells in PB, MPB, UCB, and BM. Preclinical Lin depletion can be performed under GMP conditions from PB apheresis procedures.
Similar articles
- The composition of CD34 subpopulations differs between bone marrow, blood and cord blood.
Fritsch G, Stimpfl M, Kurz M, Printz D, Buchinger P, Fischmeister G, Hoecker P, Gadner H. Fritsch G, et al. Bone Marrow Transplant. 1996 Feb;17(2):169-78. Bone Marrow Transplant. 1996. PMID: 8640162 - Characterization of a lineage-negative stem-progenitor cell population optimized for ex vivo expansion and enriched for LTC-IC.
Forraz N, Pettengell R, McGuckin CP. Forraz N, et al. Stem Cells. 2004;22(1):100-8. doi: 10.1634/stemcells.22-1-100. Stem Cells. 2004. PMID: 14688396 - Rhodamine 123 efflux in human subpopulations of hematopoietic stem cells: comparison between bone marrow, umbilical cord blood and mobilized peripheral blood CD34+ cells.
Wagner-Souza K, Diamond HR, Ornellas MH, Gomes BE, Almeida-Oliveira A, Abdelhay E, Bouzas LF, Rumjanek VM. Wagner-Souza K, et al. Int J Mol Med. 2008 Aug;22(2):237-42. Int J Mol Med. 2008. PMID: 18636179 - [Umbilical cord blood as a source of stem cells].
Bojanić I, Golubić Cepulić B. Bojanić I, et al. Acta Med Croatica. 2006 Jun;60(3):215-25. Acta Med Croatica. 2006. PMID: 16933834 Review. Croatian.
Cited by
- Effects of linagliptin on endothelial function and postprandial lipids in coronary artery disease patients with early diabetes: a randomized, placebo-controlled, double-blind trial.
Tripolt NJ, Aberer F, Riedl R, Url J, Dimsity G, Meinitzer A, Stojakovic T, Aziz F, Hödl R, Brachtl G, Strunk D, Brodmann M, Hafner F, Sourij H. Tripolt NJ, et al. Cardiovasc Diabetol. 2018 May 17;17(1):71. doi: 10.1186/s12933-018-0716-x. Cardiovasc Diabetol. 2018. PMID: 29773079 Free PMC article. Clinical Trial. - Selection of Tissue Factor-Deficient Cell Transplants as a Novel Strategy for Improving Hemocompatibility of Human Bone Marrow Stromal Cells.
Oeller M, Laner-Plamberger S, Hochmann S, Ketterl N, Feichtner M, Brachtl G, Hochreiter A, Scharler C, Bieler L, Romanelli P, Couillard-Despres S, Russe E, Schallmoser K, Strunk D. Oeller M, et al. Theranostics. 2018 Feb 4;8(5):1421-1434. doi: 10.7150/thno.21906. eCollection 2018. Theranostics. 2018. PMID: 29507631 Free PMC article. - A robust potency assay highlights significant donor variation of human mesenchymal stem/progenitor cell immune modulatory capacity and extended radio-resistance.
Ketterl N, Brachtl G, Schuh C, Bieback K, Schallmoser K, Reinisch A, Strunk D. Ketterl N, et al. Stem Cell Res Ther. 2015 Dec 1;6:236. doi: 10.1186/s13287-015-0233-8. Stem Cell Res Ther. 2015. PMID: 26620155 Free PMC article. - Oxygen sensing mesenchymal progenitors promote neo-vasculogenesis in a humanized mouse model in vivo.
Hofmann NA, Ortner A, Jacamo RO, Reinisch A, Schallmoser K, Rohban R, Etchart N, Fruehwirth M, Beham-Schmid C, Andreeff M, Strunk D. Hofmann NA, et al. PLoS One. 2012;7(9):e44468. doi: 10.1371/journal.pone.0044468. Epub 2012 Sep 7. PLoS One. 2012. PMID: 22970226 Free PMC article. - Pro-angiogenic induction of myeloid cells for therapeutic angiogenesis can induce mitogen-activated protein kinase p38-dependent foam cell formation.
Rohde E, Schallmoser K, Reinisch A, Hofmann NA, Pfeifer T, Fröhlich E, Rechberger G, Lanzer G, Kratky D, Strunk D. Rohde E, et al. Cytotherapy. 2011 Apr;13(4):503-12. doi: 10.3109/14653249.2010.536214. Epub 2010 Dec 3. Cytotherapy. 2011. PMID: 21128706 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous