Importance of Parenchymal: Stromal Cell Ratio for the Ex Vivo Reconstitution of Human Hematopoiesis

Koller, Manfred R.; Manchel, Ilana; Palsson, Bernhard Ø.

doi:10.1002/stem.150305

Cited by 38 publications

(26 citation statements)

References 40 publications

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“…61 These preclinical studies identify further UCB graft engineering questions including the role of accessory lymphoid populations in ex vivo expanded allogeneic grafts, [62][63][64][65][66] as well as the role of stromal elements in maintaining immature stem cells with self-renewal capacity during expansion. [67][68][69][70] In summary, banked unrelated umbilical cord blood (UCB) has emerged as a substitute allogeneic stem cell source, due to the lack of available HLA-matched related donors for patients requiring allogeneic transplantation, and the observed increased incidence and severity of acute and chronic GVHD when alternative HLA-matched unrelated or partially mismatched family member grafts are utilized. Early clinical reports of UCB transplantation have focused primarily on pediatric or small stature adult recipients.…”

Section: Future Initiatives: Ucb Transplantationmentioning

confidence: 99%

Umbilical cord blood for allogeneic transplantation in children and adults

Laughlin

2001

Bone Marrow Transplant

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Summary:Early clinical reports outlining outcomes for primarily pediatric patients undergoing UCB transplantation, point to delayed time to hematopoietic recovery, and favorable incidence and severity of graft-versus-host disease. Intensive clinical and laboratory research is ongoing focused on strategies to foster UCB allogeneic donor engraftment, thereby allowing wider application of this stem cell source for patients requiring allogeneic transplantation. Bone Marrow Transplantation (2001) 27, 1-6. Keywords: umbilical cord blood; allogeneic transplantation Allogeneic blood and bone marrow stem cell transplantation is limited by the availability of suitable HLAmatched related donors. In 1988, umbilical cord blood (UCB) hematopoietic stem cells (HSC) from a related sibling were transplanted successfully into a child with Fanconi anemia. 1 Subsequently, UCB from HLA-mismatched related 2 and unrelated donors has been shown to successfully engraft pediatric 3-8 and a few reported adult patients 6,9-11 with hematologic malignancies, immunodeficiency syndromes, inborn errors of metabolism, or marrow failure syndromes. This article will review the use of UCB as a suitable alternative for allogeneic transplantation. Tables 1 and 2 outline the advantages and disadvantages for the application of UCB as a new source of HSC for patients requiring allogeneic transplantation. UCB collection and bankingSince the first successful unrelated UCB transplant was performed by J Kurtzberg and the pediatric transplant team at Duke University in 1993, 7 clinical and laboratory studies have burgeoned and standard operating procedures have been developed for the collection, processing, and storage of UCB units. [12][13][14][15][16][17][18][19] UCB collection is performed during the final phase of labor or, more commonly, after delivery of

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Section: Future Initiatives: Ucb Transplantationmentioning

confidence: 99%

Umbilical cord blood for allogeneic transplantation in children and adults

Laughlin

2001

Bone Marrow Transplant

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“…Expansion of HSCs in vitro is still limited in extent and duration, and the expansion technology has not yet reached a stage where ex vivo-expanded hematopoietic progenitors and stem cells can be used routinely for replacement therapy. [6][7][8][9] Another alternative strategy to overcome those limitations associated with HSCT is to identify and use stem cells from nonlymphoid tissues, which might be easier to maintain and expand in vitro and which possess hematopoietic potential such as embryonic stem cells (ESCs), 10,11 neural stem cells (NSCs), 12 and muscle stem cells. 13,14 Mouse NSCs can easily be isolated and propagated in vitro for prolonged periods (approximately 1 year), resulting in a 10 7 -fold increase in cell number, without losing their proliferative and multilineage potential.…”

Section: Introductionmentioning

confidence: 99%

Identification of a candidate human neurohematopoietic stem-cell population

Shih

Weng

Mamelak

et al. 2001

Blood

109

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It was recently reported that transplantation of clonally derived murine neurosphere cells into sublethally irradiated allogeneic hosts leads to a donor-derived hematopoietic reconstitution. The confirmation of the existence of a common neurohematopoietic stem cell in the human brain will have a significant effect on stem cell research and on clinical transplantation. Here, it is demonstrated that the human fetal brain contains separate but overlapping epidermal growth factor (EGF)-responsive and basic fibroblast growth factor (FGF-2)-responsive neural stem cells. The majority (> 85%) of cells within these EGF-and/or FGF-2-generated neurospheres express characteristic neural stem/progenitor cell markers including nestin, EGF receptor, and FGF-2 receptor. These neural stem cells can be continuously passaged in vitro, and demonstrate a constant 20-fold expansion in every passage for up to the fifth passage (the longest period that has been carried out in the authors' laboratory). These neural stem cells are multipotential for neurons, astrocytes, and oligodendrocytes. After transplantation into SCID-hu mice, all neural stem cells, regardless of passages, culture conditions, and donors, are able to establish long-term hematopoietic reconstitution in the presence of an intact human bone marrow microenvironment.( IntroductionHematopoietic stem cell transplantation (HSCT) has been shown to provide a definitive benefit for a variety of malignant and nonmalignant hematologic diseases and myelopoietic support for patients undergoing high-dose chemotherapy. 1,2 Several inherent limitations associated with HSCT, however, have restricted its general use. 3,4 These include (1) a lack of sufficient donors for all recipients, (2) a requirement of either operative bone marrow (BM) harvests or pheresis procedures to obtain sufficient stem cells necessary for benefit after transplantation, and (3) the potential for tumor contamination in autologous HSCT. A straightforward strategy to overcome these limitations is to develop culture systems for ex vivo expansion of transplantable hematopoietic stem cells (HSCs). 5 Ex vivo-generated and -expanded HSCs could support multiple cycles of chemotherapy, provide transplantation options for patients without matched donors, facilitate transduction of vectors into HSCs for gene therapy, and provide a tumor-free product for transplantation. During the last 10 years, better ways to identify and purify HSCs and the availability of various cytokines have facilitated and improved the development of ex vivo stem cell expansion technology. Expansion of HSCs in vitro is still limited in extent and duration, and the expansion technology has not yet reached a stage where ex vivo-expanded hematopoietic progenitors and stem cells can be used routinely for replacement therapy. [6][7][8][9] Another alternative strategy to overcome those limitations associated with HSCT is to identify and use stem cells from nonlymphoid tissues, which might be easier to maintain and expand in vitro and which possess hemat...

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“…Novel tissue engineering applications involve the coculturing of different cell types to achieve a functional tissue or organ (e.g., Koller et al, 1997, for hematopoietic tissue). The introduction of different cell types inside the bioreactor can introduce several levels of complexities in the design and operation of the bioreactor in terms of sustained viability, growth, and function of all the cell types.…”

Section: Effect Of Cell Type Heterogeneitymentioning

confidence: 99%

“…The ability to maintain a composition of cells in proliferating cell cultures can prove to be crucial in some important tissue engineering applications for example in culturing primary cells consisting of adult stem cells (Koller et al, 1997). Primary cells are inherently heterogeneous and adult stem cells form a very small percentage (<0.001%) of the cell population.…”

Section: Effect Of Cell Type Heterogeneitymentioning

confidence: 99%

Model‐based analysis and design of a microchannel reactor for tissue engineering

Mehta

Linderman

2006

Biotech & Bioengineering

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Recently developed perfusion micro-bioreactors offer the promise of more physiologic in vitro systems for tissue engineering. Successful application of such bioreactors will require a method to characterize the bioreactor environment required to elicit desired cell function. We present a mathematical model to describe nutrient/growth factor transport and cell growth inside a microchannel bioreactor. Using the model, we first show that the nature of spatial gradients in nutrient concentration can be controlled by both design and operating conditions and are a strong function of cell uptake rates. Next, we extend our model to investigate the spatial distributions of cell-secreted soluble autocrine/paracrine growth factors in the bioreactor. We show that the convective transport associated with the continuous cell culture and possible media recirculation can significantly alter the concentration distribution of the soluble signaling molecules as compared to static culture experiments and hence needs special attention when adapting static culture protocols for the bioreactor. Further, using an unsteady state model, we find that spatial gradients in nutrient/growth factor concentrations can bring about spatial variations in the cell density distribution inside the bioreactor, which can result in lowered working volume of the bioreactor. Finally, we show that the nutrient and spatial limitations can dramatically affect the composition of a co-cultured cell population. Our results are significant for the development, design, and optimization of novel micro-channel systems for tissue engineering.

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Importance of Parenchymal: Stromal Cell Ratio for the Ex Vivo Reconstitution of Human Hematopoiesis

Cited by 38 publications

References 40 publications

Umbilical cord blood for allogeneic transplantation in children and adults

Umbilical cord blood for allogeneic transplantation in children and adults

Identification of a candidate human neurohematopoietic stem-cell population

Model‐based analysis and design of a microchannel reactor for tissue engineering

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