Three-Stage<i>Ex Vivo</i>Expansion of High-Ploidy Megakaryocytic Cells: Toward Large-Scale Platelet Production

Panuganti, Swapna; Schlinker, Alaina C.; Lindholm, Paul F.; Papoutsakis, Eleftherios T.; Miller, William M.

doi:10.1089/ten.tea.2011.0111

Cited by 58 publications

(95 citation statements)

References 71 publications

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“…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%

“…Mature MKs can reach 128 N in the body and release thousands of platelets per mature MK (Deutsch and Tomer 2006) whereas mature MKs derived from an in vitro culture rarely attain 64 N and produce less than a hundred platelets per cell (Mattia et al 2002). Several methods have been proposed to enhance megakaryopoiesis of HSCs, such as the addition of cytokine cocktails (Panuganti et al 2013;van den Oudenrijn et al 1999), chemical treatment (Avanzi et al 2012;Giammona et al 2006;Lannutti et al 2005) and oxidative stress (Mostafa et al 2000;Ojima et al 2013). These methods can improve the in vitro megakaryopoesis as confirmed by the increase in MK surface marker expression and the promoted polyploidization to up to 50 % of polyploid MKs after a week of culturing.…”

Section: Low Efficiency Of Megakaryopoiesismentioning

confidence: 99%

“…HSCs are the progenitor cells for all blood cell types including leukocytes, erythrocytes and platelets (Akashi et al 2000) and can be specifically directed into the megakaryopoiesis upon interaction with thrombopoietin (TPO) (Deutsch and Tomer 2006). In addition to TPO, various cytokines have been identified as stimulating factors during megakaryopoiesis, including interleukin (IL)-3, IL-6, IL-9 (Chen et al 2009a, b), IL-11 and stem cell factor (SCF) (Teramura et al 1992;Panuganti et al 2013). Although the absence of these cytokines does not prevent the progress of TPOinduced megakaryopoiesis, the addition of cytokines has been reported to stimulate megakaryopoiesis (Deutsch and Tomer 2006;Panuganti et al 2013).…”

Section: Introductionmentioning

confidence: 99%

“…In addition to TPO, various cytokines have been identified as stimulating factors during megakaryopoiesis, including interleukin (IL)-3, IL-6, IL-9 (Chen et al 2009a, b), IL-11 and stem cell factor (SCF) (Teramura et al 1992;Panuganti et al 2013). Although the absence of these cytokines does not prevent the progress of TPOinduced megakaryopoiesis, the addition of cytokines has been reported to stimulate megakaryopoiesis (Deutsch and Tomer 2006;Panuganti et al 2013). SCF plays an important role for increasing cell proliferation in early megakaryopoiesis (Chang et al 2007).…”

Section: Introductionmentioning

confidence: 99%

“…SCF plays an important role for increasing cell proliferation in early megakaryopoiesis (Chang et al 2007). IL-3 has a synergistic effect with TPO on promoting megakaryopoiesis, whereas the benefit of IL-6 or IL-11 remains unclear (Panuganti et al 2013). …”

Section: Introductionmentioning

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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Section: Low Hsc Expansionmentioning

confidence: 99%

Section: Low Efficiency Of Megakaryopoiesismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Recent developments in ex vivo platelet production

2016

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Design‐of‐Experiments for Development and Optimization of Bioreactor Media

Mandenius

2016

Bioreactors

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Separation of in‐vitro‐derived megakaryocytes and platelets using spinning‐membrane filtration

Schlinker

Radwanski

Wegener

et al. 2014

Biotech & Bioengineering

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In-vitro-derived platelets (PLTs) could potentially overcome problems associated with donated PLTs, including contamination and alloimmunization. Although several groups have produced functional PLTs from stem cells in vitro, the challenge of developing this technology to yield transfusable PLT units has yet to be addressed. The asynchronous nature of in vitro PLT generation makes a single harvest point infeasible for collecting PLTs as soon as they are formed. The current standard of performing manual centrifugations to separate PLTs from nucleated cells at multiple points during culture is labor-intensive, imprecise, and difficult to standardize in accordance with current Good Manufacturing Practices (cGMP). In an effort to develop a more effective method, we adapted a commercially-available, spinning-membrane filtration device to separate in-vitro-derived PLTs from nucleated cells and recover immature megakaryocytes (MKs), the precursor cells to PLTs, for continued culture. Processing a mixture of in-vitro-derived MKs and PLTs on the adapted device yielded a pure PLT population and did not induce PLT pre-activation. MKs recovered from the separation process were unaffected with respect to viability and ploidy, and were able to generate PLTs after reseeding in culture. Being able to efficiently harvest in-vitro-derived PLTs brings this technology one step closer to clinical relevance.

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Three-StageEx VivoExpansion of High-Ploidy Megakaryocytic Cells: Toward Large-Scale Platelet Production

Cited by 58 publications

References 71 publications

Recent developments in ex vivo platelet production

Recent developments in ex vivo platelet production

Design‐of‐Experiments for Development and Optimization of Bioreactor Media

Separation of in‐vitro‐derived megakaryocytes and platelets using spinning‐membrane filtration

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