Ex Vivo Large‐Scale Generation of Human Platelets from Cord Blood CD34
            <sup>+</sup>
            Cells

Matsunaga, Takuya; Tanaka, Ikuta; Kobune, Masayoshi; Kawano, Yutaka; Tanaka, Maki; Kuribayashi, Kageaki; Iyama, Satoshi; Sato, Tsutomu; Sato, Yasushi; Takimoto, Rishu; Takayama, Tetsuji; Kato, Junji; Ninomiya, Takafumi; Hamada, Hirofumi; Niitsu, Yoshiro

doi:10.1634/stemcells.2006-0309

Cited by 120 publications

(120 citation statements)

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“…1 Numerous investigators have tried to increase CB stem cell numbers by culturing CD34 ϩ cells ex vivo under a variety of culture conditions; these attempts have, however, met with limited success. [2][3][4][5][6][7][8][9][10][11][12][13] CBHSCs/HPCs have also been used to generate alternative sources of terminally differentiated blood cells for use as transfusion products. 4,8 Adult blood HSCs/HPCs, human embryonic stem cells (ES) as well as induced pluripotent stem cells (iPS) have also been used for this same purpose.…”

Section: Introductionmentioning

confidence: 99%

Chromatin-modifying agents promote the ex vivo production of functional human erythroid progenitor cells

Chaurasia

Berenzon

Hoffman

2011

Blood

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IntroductionCord blood (CB) cells are an effective source of pluripotent hematopoietic stem and progenitor cells (HSCs/HPCs) that can be used to hematologically reconstitute patients who have received myeloablative chemotherapy and/or radiation therapy. 1 Numerous investigators have tried to increase CB stem cell numbers by culturing CD34 ϩ cells ex vivo under a variety of culture conditions; these attempts have, however, met with limited success. 2-13 CBHSCs/HPCs have also been used to generate alternative sources of terminally differentiated blood cells for use as transfusion products. 4,8 Adult blood HSCs/HPCs, human embryonic stem cells (ES) as well as induced pluripotent stem cells (iPS) have also been used for this same purpose. 4,8,14,15 All presently available TPs are composed of terminally differentiated cells with a finite life span. 2,4,8 HPCs retain their capacity to undergo repeated divisions allowing them to produce greater numbers of blood cells belonging to a particular lineage. The use of HPCs as a TP would represent a major paradigm shift because they would continue to generate differentiated cells for a prolonged period of time. The major obstacle to the creation of such a TP is the lack of sufficient numbers of HSCs/HPCs from a readily accessible sources. [16][17][18] Recently, a variety of epigenetic events including the methylation of gene promoter regions as well as transcriptional inhibitory complexes such as histone deacetylases and certain histone methylases have been shown to influence HSC fate decisions. 19,20 Chromatin-modifying agents (CMAs) such as HDACIs and DNA methyltransferase inhibitors (DNMTIs) comprise a structurally diverse group of compounds which are capable of regulating chromatin remodeling and influencing gene expression patterns. 21,22 Our laboratory has sequentially treated both adult marrow and CB-CD34 ϩ cells with a DNMTI followed by an HDACI in vitro resulting in an increase in the numbers of human marrow repopulating cells (MRCs). 23,24 The use of such small molecules to alter normal HSC/HPC fate decisions has been confirmed by several additional laboratories. 13,19,[25][26][27] We hypothesize that a particular combination of cytokines and an HDACI might be useful to promote erythroid commitment of CB-CD34 ϩ cells. Methods Isolation of CB-CD34 ؉ cellsFresh CB collections were obtained from the Placental Blood Program at the New York Blood Center (New York, NY) according to guidelines established by the Mount Sinai School of Medicine Institutional Review Board. Low-density CB-mononuclear cells (MNCs) were isolated by density centrifugation and CD34 ϩ cells were isolated as previously described. 23 Highly purified CB-CD34 ϩ cells (90%-98%) were used for all experiments. Ex vivo cultureHuman CB-CD34 ϩ cells (1 ϫ 10 5 /mL) were cultured in Iscove modified Dulbecco medium (IMDM; Lonza) containing 30% FBS (HyClone Laboratories) supplemented with 100 ng/mL SCF, 100 ng/mL Flt3 ligand (FL), 100 ng/mL Tpo, and 50 ng/mL IL-3 (cytokines were a gift of Amgen) and incubated in...

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Section: Introductionmentioning

confidence: 99%

Chromatin-modifying agents promote the ex vivo production of functional human erythroid progenitor cells

Chaurasia

Berenzon

Hoffman

2011

Blood

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“…By employing this technique, the requirement for seeded MK progenitors can be reduced. To our knowledge, Matsunaga et al (2006) reported the highest yields of platelet per seeded HSC, generating 1.26-1.68 9 10 11 platelets from 5 9 10 6 HSCs (amount of CB-derived HSCs per donor).…”

Section: Low Efficiency Of Megakaryopoiesismentioning

confidence: 92%

“…PB-derived HSCs are preferable for generating platelets but the proliferation capacity is reduced once the cells are committed into megakaryopoiesis. Therefore, a multiphase culture system was proposed to allow successive goals: extensive HSC expansion, optimized MK maturation, and promotion of platelet formation (Matsunaga et al 2006;Panuganti et al 2013). Nevertheless, this strategy is applicable only to a single platelet production process.…”

Section: Low Hsc Expansionmentioning

confidence: 99%

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Recent developments in ex vivo platelet production

2016

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The platelet is a component of blood that functions to initiate blood clotting. Abnormal platelet count and function can lead to a life-threatening condition caused by excessive bleeding. At present, platelet supply for transfusion can be obtained only from platelet donation. However, platelets cannot be stored for longer than 7 days, meaning that routine isolation is required to maintain platelet supply for transfusion. To mitigate for potential platelet shortages, several strategies have been proposed to generate platelets ex vivo. By employing both of natural and artificial approaches, several researchers have successfully generated biomaterials with characteristics similar to human-derived platelets. Their reports indicated that the biomaterials could mimic the aggregation of human-isolated platelets, further suggesting the possibility to substitute or complement human-isolated platelets. The current review summarizes the progress in ex vivo platelet production and gives a prospect for the possible approaches to achieving a feasible platelet factory, based on the Good Manufacturing Practice standards.

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“…It is also possible to renovate the entire blood system transplanting hematopoietic stem cells (HSC) to allow a full recovery of the hematopoietic system in patients with different hematological disorders such as aplastic anemia and leukemia. This approach opened a wide range of clinical applications for progenitor blood cells transplantation including gene therapy (Zubler 2006) and the generation of specific mature cell types (Matsunaga et al 2006;Introna et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Expansion of human hematopoietic stem cells for transplantation: trends and perspectives

2008

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Umbilical cord blood transplantation is clinically limited by its low progenitor cell content. Ex vivo expansion has become an alternative to increase the cell dose available for transplants. Expansion has been evaluated in several ways such as static cultures combining growth factors or mimicking the natural microenvironment using co-culture systems. However, static cultures have a small volume capacity and therefore large-scale expansion has been addressed using bioreactors. These and other biotechnological approaches for the expansion of hematopoietic progenitors and their utility to study several aspects of hematopoietic stem cell biology are discussed here.

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Ex Vivo Large‐Scale Generation of Human Platelets from Cord Blood CD34 ⁺ Cells

Abstract: In the present investigation, we generated platelets (PLTs) from cord blood (CB) CD34؉ cells using a three-phase culture system. We first cultured 500 CB CD34

Cited by 120 publications

References 43 publications

Chromatin-modifying agents promote the ex vivo production of functional human erythroid progenitor cells

Chromatin-modifying agents promote the ex vivo production of functional human erythroid progenitor cells

Recent developments in ex vivo platelet production

Expansion of human hematopoietic stem cells for transplantation: trends and perspectives

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Ex Vivo Large‐Scale Generation of Human Platelets from Cord Blood CD34 + Cells

Abstract: In the present investigation, we generated platelets (PLTs) from cord blood (CB) CD34؉ cells using a three-phase culture system. We first cultured 500 CB CD34

Cited by 120 publications

References 43 publications

Chromatin-modifying agents promote the ex vivo production of functional human erythroid progenitor cells

Chromatin-modifying agents promote the ex vivo production of functional human erythroid progenitor cells

Recent developments in ex vivo platelet production

Expansion of human hematopoietic stem cells for transplantation: trends and perspectives

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Product

Resources

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Ex Vivo Large‐Scale Generation of Human Platelets from Cord Blood CD34 ⁺ Cells