Thrombopoietin Is Synergistic with Other Cytokines for Expansion of Cord Blood Progenitor Cells

Won, Jong Ho; Cho, Sang Deog; Park, Sung Kyu; Lee, Gyu Taeg; Baick, Seung Ho; Suh, Won Suk; Hong, Dae Sik; Park, Hee Sook

doi:10.1089/152581600419125

Cited by 15 publications

(7 citation statements)

References 33 publications

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“…Investigators around the world have studied the expansion of stem cells using various growth factors including IL-1, FLT-3L, TPO, INF-γ, alone or in different combinations in an attempt to achieve maximum expansion [14,15,16]. Increasing the amount and number of growth factors added will also considerably add to the cost per expansion.…”

Section: Discussionmentioning

confidence: 99%

Ex vivo Expansion of Umbilical Cord Blood Stem Cells Using Different Combinations of Cytokines and Stromal Cells

Madkaikar¹,

Ghosh²,

Gupta³

et al. 2007

Acta Haematol

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Umbilical cord blood is a promising source of hematopoietic stem cells (HSC) for allogeneic transplantation. However, graft rejection and delayed engraftment remain major limitations, both of which are related to a limited number of stem cells in the cord blood graft. Ex vivo expansion of HSC has been suggested as one of the ways of overcoming the challenges caused by a limited hematopoietic cell number from cord blood stem cell transplantation. In this study, we quantified and characterized an ex vivo expansion capacity of cord blood-derived HSC in a liquid culture system under different conditions. These conditions included: the combinations and concentrations of hematopoietic growth factors [stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3, IL-6 and erythropoietin (EPO)], placental conditioning medium (PCM), and stromal cell support. During culture, the mean nucleated cell count, the mean CD34+ cell count, fold expansion, viability, clonogenic assays and immunophenotypic characterization were performed on day 0, day 7, day 12 and day 14 on the expanded cellular product. The maximum expansion was achieved using GF2 (SCF + IL-3 + GM-CSF) with stromal cell support. The mean CD34+ cell expansion on days 7 and 12 was 16.25- and 21.4-fold (5.2–32), respectively, and the mean nucleated cell expansion was 15.1- and 21-fold (18.1–23.2). The mean nucleated cell viability on day 12 was 87.9% (85.6–92.5). After 12 days, granulocyte-macrophage colony-forming units CFU-GEMM showed a 20.4-fold increase. A 21.4-fold increase in the CD34+ cells and a 20-fold increase in the CFU-GEMM should provide enough cells from a single cord blood unit to reduce the period of cytopenia after single unit cord blood transplantation. Even if there was some doubt about the long-term repopulating capacity of the expanded cells part of the collected umbilical cord cells (25%) could be expanded till day 12 after transplanting the major part (75%) of the collection.

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Section: Discussionmentioning

confidence: 99%

Ex vivo Expansion of Umbilical Cord Blood Stem Cells Using Different Combinations of Cytokines and Stromal Cells

Madkaikar¹,

Ghosh²,

Gupta³

et al. 2007

Acta Haematol

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“…However, the addition of FCS in culture affects colony growth in an uncontrolled manner, because it contains growth and inhibitory molecules [4]. Various semisolid matrix materials like fibrin clots, agar and collagen in combination with recombinant cytokines, most importantly IL-3, IL-6, IL-1, stem cell factor and thrombopoietin have been used for the development of serum-free systems for quantification of Mk colonies [3,4,5,6,7,8]. …”

Section: Discussionmentioning

confidence: 99%

Assessment of Megakaryopoiesis in Children with Acute Lymphoblastic Leukemia

et al. 2005

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The effect of the underlying disease and chemotherapy on megakaryopoiesis has not been extensively studied in children with acute lymphoblastic leukemia (ALL) during and at the end of therapy. Using a serum-free assay, we assessed the megakaryocyte (Mk) colony formation in vitro from bone marrow mononuclear cells of 25 children with ALL during chemotherapy and shortly after the cessation of it. Twelve children with solid tumors without bone marrow involvement and cord blood from 10 full-term normal vaginal deliveries were used as controls. A significant reduction in the number of Mk colonies was observed at diagnosis of ALL, and Mk colony formation remained lower than controls throughout the different phases of leukemia treatment. Our study suggests that defects in megakaryopoiesis of children with ALL in long-term remission may persist during chemotherapy and at least shortly after the end of it.

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“…However, IL-3 may be detrimental to the pluripotentiality of murine progenitors (Matsunaga et al 1998), and when added in inappropriately high concentration to human progenitors it induces terminal differentiation of HPCs (Zandstra et al 1997). Similar to the actions of SCF, TPO supports the proliferation and long-term maintenance of primitive haematopoietic progenitors and repopulating HSCs when used in combination with other stimulatory cytokines or in the presence of stroma (Kobayashi et al 1996;Won et al 2000;Yagi et al 1999) but has little effect on the expansion of HSCs in suspension cultures when used alone (Kobayashi et al 1997).…”

Section: Culture Mediamentioning

confidence: 99%