Ex vivo expansion of cord blood mononuclear cells on mesenchymal stem cells

McNiece, Ian; Harrington, Jr. Joseph E.; Turney, Jennifer; Kellner, Joshua; Shpall, Elizabeth J.

doi:10.1080/14653240410004871

Cited by 137 publications

(107 citation statements)

References 5 publications

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“…CB hematopoietic stem/progenitor cells are also used for research in various fields of biological science, such as drug sensitivity (Gribaldo et al 1999) or radiation sensitivity (Kashiwakura et al 2000(Kashiwakura et al , 2002(Kashiwakura et al , 2006aMonzen et al 2006). Furthermore, mesenchymal stem cells and somatic stem cells contained in CB have already been applied for bio-medical therapies and research in regenerative medicine (Kögler et al 2004;McNiece et al 2004;Hirata et al 2005;Ma et al 2005;Pozzi et al 2006). The importance of CB has therefore greatly increased as a source for both clinical and basic scientific research.…”

Section: Cb Units Collected For Subjectsmentioning

confidence: 99%

Maternal and Neonatal Factors Associated with the High Yield of Mononuclear Low-Density/CD34+ Cells from Placental/Umbilical Cord Blood

Omori

Takahashi

Hazawa

et al. 2008

Tohoku J. Exp. Med.

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Placental/umbilical cord blood (CB) contains nucleated cells and hematopoietic stem/ progenitor cells (CD34 + cells). However it is difficult to predict the number of nucleated/ CD34 + cells in each CB before cell processing. Despite many previous studies from institutes affiliated with CB banks in metropolitan areas, little information is available regarding the characteristics of CB units from other medical facilities. The purpose of the present study was to analyze the maternal/neonatal factors on the yield of cells in CB units. A total of 176 CB units were obtained from single-birth and normal vaginal deliveries. Mononuclear low-density (LD) cells were separated using Ficoll-Paque within 24 hrs after CB collection and then processed for the purification of CD34 + cells. A multiple linear regression analysis was performed to assess the correlations between the yield of cells and maternal/neonatal factors including maternal age, gravid status, duration of labor, gestational age, neonatal height and weight, cord length, and meconium in the amniotic fluid. The total LD cells per CB unit had a weak positive correlation with the maternal age of primigravidae. The total LD cells per CB unit from the primigravidae aged 25 were significantly higher than those from the primigravidae aged 24. The total CD34 + cells per CB unit from the 1-gravidae were significantly higher than those from the 2-gravidae and 3-gravidae, respectively among all donors. These results indicate that the CB units from the primigravidae aged 25 are more likely to contain higher yield of LD/CD34 + cells. cord blood; mononuclear cells; CD34 + cells; maternal/neonatal factors.Tohoku

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Section: Cb Units Collected For Subjectsmentioning

confidence: 99%

Maternal and Neonatal Factors Associated with the High Yield of Mononuclear Low-Density/CD34+ Cells from Placental/Umbilical Cord Blood

Omori

Takahashi

Hazawa

et al. 2008

Tohoku J. Exp. Med.

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“…66 Third-party MSC can be used to alleviate donor deviation in dual-cord transplantation and to facilitate engraftment of multidonor UCBT as shown in NOD/SCID mice. [67][68][69] It is unclear whether the immunomodulatory properties of MSC 70,71 when cocultured with unmanipulated cord cells yielding a 16-37-fold increase in CD34 þ cells 72 will prove useful in the setting of cord blood transplant or adoptive immunotherapy.…”

Section: Stromamentioning

confidence: 99%

Ex vivo expansion of umbilical cord blood stem cells for transplantation: growing knowledge from the hematopoietic niche

Hofmeister

Zhang

Knight

et al. 2006

Bone Marrow Transplant

203

172

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Umbilical cord blood transplantation (UCBT) in adults is limited by the small number of primitive hematopoietic stem cells (HSC) in each graft, resulting in delayed engraftment post transplant, and both short-and longterm infectious complications. Initial efforts to expand UCB progenitors ex vivo have resulted in expansion of mature rather than immature HSC, confounded by the inability to accurately and reliably measure long-term reconstituting cells. Ex vivo expansion of UCB HSC has failed to improve engraftment because of resulting defects that promote apoptosis, disrupt marrow homing and initiate cell cycling. Here we discuss the future of ex vivo expansion, which we suggest will include the isolation of immature hematopoietic progenitors on the basis of function rather than surface phenotype and will employ both cytokines and stroma to maintain and expand the stem cell niche. We suggest that ex vivo expansion could be enhanced by manipulating newly discovered signaling pathways (Notch, Wnt, bone morphogenetic protein 4 and Tie2/angiopoietin-1) and intracellular mediators (phosphatase and tensin homolog and glycogen synthase kinase-3) in a manner that promotes HSC expansion with less differentiation. Improved methods for ex vivo expansion will make UCBT available to more patients, decrease engraftment times and allow more rapid immune reconstitution post transplant.

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“…These newer approaches have all shown great potential for the ex vivo expansion of CB‐HSPC or accelerating their engraftment. Still, expansion of the true hematopoietic stem cell pool has been limited 2, 4, 45, 46. We 4, 5, 6, 7 and others 38 have previously shown that CB‐HSPC can be effectively expanded and driven to differentiate toward both the myeloid and lymphoid lineages in a serum‐free culture system, using a feeder layer of adult human BM‐derived stromal cells.…”

Section: Discussionmentioning

confidence: 96%

Evaluating Interaction of Cord Blood Hematopoietic Stem/Progenitor Cells with Functionally Integrated Three-Dimensional Microenvironments

Mokhtari

Baptista

Vyas

et al. 2018

Stem Cells Translational Medicine

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Despite advances in ex vivo expansion of cord blood‐derived hematopoietic stem/progenitor cells (CB‐HSPC), challenges still remain regarding the ability to obtain, from a single unit, sufficient numbers of cells to treat an adolescent or adult patient. We and others have shown that CB‐HSPC can be expanded ex vivo in two‐dimensional (2D) cultures, but the absolute percentage of the more primitive stem cells decreases with time. During development, the fetal liver is the main site of HSPC expansion. Therefore, here we investigated, in vitro, the outcome of interactions of primitive HSPC with surrogate fetal liver environments. We compared bioengineered liver constructs made from a natural three‐dimensional‐liver‐extracellular‐matrix (3D‐ECM) seeded with hepatoblasts, fetal liver‐derived (LvSt), or bone marrow‐derived stromal cells, to their respective 2D culture counterparts. We showed that the inclusion of cellular components within the 3D‐ECM scaffolds was necessary for maintenance of HSPC viability in culture, and that irrespective of the microenvironment used, the 3D‐ECM structures led to the maintenance of a more primitive subpopulation of HSPC, as determined by flow cytometry and colony forming assays. In addition, we showed that the timing and extent of expansion depends upon the biological component used, with LvSt providing the optimal balance between preservation of primitive CB HSPC and cellular differentiation. Stem Cells Translational Medicine 2018;7:271–282

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Ex vivo expansion of cord blood mononuclear cells on mesenchymal stem cells

Cited by 137 publications

References 5 publications

Maternal and Neonatal Factors Associated with the High Yield of Mononuclear Low-Density/CD34+ Cells from Placental/Umbilical Cord Blood

Maternal and Neonatal Factors Associated with the High Yield of Mononuclear Low-Density/CD34+ Cells from Placental/Umbilical Cord Blood

Ex vivo expansion of umbilical cord blood stem cells for transplantation: growing knowledge from the hematopoietic niche

Evaluating Interaction of Cord Blood Hematopoietic Stem/Progenitor Cells with Functionally Integrated Three-Dimensional Microenvironments

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