Generation of Induced Pluripotent Stem Cells from Human Cord Blood

Haase, Alexandra; Olmer, Ruth; Schwanke, Kristin; Wunderlich, Stephanie; Merkert, Sylvia; Heß, Christian; Zweigerdt, Robert; Gruh, Ina; Meyer, Johann; Wagner, Stefan; Maier, Lars S.; Han, Dong Wook; Glage, Silke; Miller, Konstantin; Fischer, Philipp; Schöler, Hans R.; Martin, Ulrich

doi:10.1016/j.stem.2009.08.021

Cited by 436 publications

(315 citation statements)

References 14 publications

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“…The human iPSC line hCBiPSC2 was derived from human cord blood endothelial cells, as previously described (17). iPSCs were adapted to feeder-and xeno-free culture by transfer onto human recombinant Laminin-521-coated plates (BioLamina) and using StemMACS medium (Miltenyi Biotech).…”

Section: Materials and Methods Generation And Culture Of Hla-universamentioning

confidence: 99%

Generation of HLA-Universal iPSC-Derived Megakaryocytes and Platelets for Survival Under Refractoriness Conditions

Börger

Eicke

Wolf

et al. 2016

Mol Med

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Platelet (PLT) transfusion is indispensable to maintain homeostasis in thrombocytopenic patients. However, PLT transfusion refractoriness is a common life-threatening condition observed in multitransfused patients. The most frequent immune cause for PLT transfusion refractoriness is the presence of alloantibodies specific for human leukocyte antigen (HLA) class I epitopes. Here, we have silenced the expression of HLA class I to generate a stable HLA-universal induced pluripotent stem cell (iPSC) line that can be used as a renewable cell source for the generation of low immunogenic cell products. The expression of HLA class I was silenced by up to 82% and remained stable during iPSC cultivation. In this study, we have focused on the generation of megakaryocytes (MK) and PLTs from a HLA-universal iPSC source under feeder-and xeno-free conditions. On d 19, differentiation rates of MKs and PLTs with means of 58% and 76% were observed, respectively. HLA-universal iPSC-derived MKs showed polyploidy with DNA contents higher than 4n and formed proPLTs. Importantly, differentiated MKs remained silenced for HLA class I expression. HLA-universal MKs produced functional PLTs. Notably, iPSC-derived HLA-universal MKs were capable to escape antibody-mediated complement-and cellular-dependent cytotoxicity. Furthermore, HLA-universal MKs were able to produce PLTs after in vivo transfusion in a mouse model indicating that they might be used as an alternative to PLT transfusion. Thus, in vitro produced low immunogenic MKs and PLTs may become an alternative to PLT donation in PLT-based therapies and an important component in the management of severe alloimmunized patients.

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Section: Materials and Methods Generation And Culture Of Hla-universamentioning

confidence: 99%

Generation of HLA-Universal iPSC-Derived Megakaryocytes and Platelets for Survival Under Refractoriness Conditions

Börger

Eicke

Wolf

et al. 2016

Mol Med

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“…Therefore, NCCs could represent a key cell source for tooth-tissue engineering. Induced pluripotent stem (iPS) cells are generated from a variety of somatic cells such as dermal fibroblasts (53,54), blood cells, (12) and dental pulp cells (42,55,59,62) by induction with several factors. iPS cells are able to differentiate into all three germ layers with large-scale expansion (12, 42, 53-55, 59, 62), bypassing the potential ethical problems of using embryonic stem (ES) cells.…”

Section: Methodsmentioning

confidence: 99%

<b>Induction of neural crest cells from human dental pulp-derived induced pluripotent stem </b><b>cells </b>

et al. 2017

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We previously generated induced pluripotent stem (iPS) cells from human dental pulp cells of deciduous teeth. Neural crest cells (NCCs) play a vital role in the development of the oral and maxillofacial region. Therefore, NCCs represent a cell source for bone, cartilage, and tooth-related tissue engineering. In this study, we examined whether iPS cells are capable of differentiating into NCCs through modification of the human embryonic stem cell protocol. First, iPS cells were dissociated into single cells and then reaggregated in low-cell-adhesion plates with neural induction medium for 8 days in suspension culture to form neurospheres. The neurospheres were transferred to fibronectin-coated dishes and formed rosette structures. The migrated cells from the rosettes abundantly expressed NCC markers, as evidenced by real-time polymerase chain reaction, immunofluorescence, and flow cytometric analysis. Furthermore, the migrated cells exhibited the ability to differentiate into neural crest lineage cells in vitro. They also exhibited tissue-forming potential in vivo, differentiating into bone and cartilage. Collectively, the migrated cells had similar characteristics to those of NCCs. These results suggest that human dental pulp cell-derived iPS cells are capable of differentiating into NCCs. Therefore, iPS cell-derived NCCs represent cell sources for bone and cartilage tissue engineering.

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“…With this in mind, the ideal cell source for cardiac tissue engineering would be patient-specific stem cell-derived cardiomyocytes. Cardiac 1 differentiation has been demonstrated successfully for both embryonic stem cells 5,6 and induced pluripotent stem cells [7][8][9][10] from various species; however, these cells are currently not suitable for clinical application in patients due to the methods used in their generation. Despite recent promising results regarding scalable expansion 11,12 and differentiation 13 of embryonic and pluripotent stem cells, the available numbers of stem cell-derived cardiac cells have not been sufficient for the generation of BCT of appropriate sizes for therapeutic application so far.…”

Section: Introductionmentioning

confidence: 99%

A Novel Miniaturized Multimodal Bioreactor for Continuous In Situ Assessment of Bioartificial Cardiac Tissue During Stimulation and Maturation

Kensah

Gruh

Viering

et al. 2011

Tissue Engineering Part C: Methods

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Stem cell-based cardiac tissue engineering is a promising approach for regenerative therapy of the injured heart. At present, the small number of stem cell-derived cardiomyocytes that can be obtained using current culture and enrichment techniques represents one of the key limitations for the development of functional bioartificial cardiac tissue (BCT). We have addressed this problem by construction of a novel bioreactor with functional features of larger systems that enables the generation and in situ monitoring of miniaturized BCTs. BCTs were generated from rat cardiomyocytes to demonstrate advantages and usefulness of the bioreactor. Tissues showed spontaneous, synchronized contractions with cell orientation along the axis of strain. Cyclic stretch induced cardiomyocyte hypertrophy, demonstrated by a shift of myosin heavy chain expression from the alpha to beta isoform, together with elevated levels of atrial natriuretic factor. Stretch led to a moderate increase in systolic force (1.42 AE 0.09 mN vs. 0.96 AE 0.09 mN in controls), with significantly higher forces observed after b-adrenergic stimulation with noradrenalin (2.54 AE 0.11 mN). Combined mechanical and b-adrenergic stimulation had no synergistic effect. This study demonstrates for the first time that mechanical stimulation and direct real-time contraction force measurement can be combined into a single multimodal bioreactor system, including electrical stimulation of excitable tissue, perfusion of the culture chamber, and the possibility of (fluorescence) microscopic assessment during continuous cultivation. Thus, this bioreactor represents a valuable tool for monitoring tissue development and, ultimately, the optimization of stem cell-based tissue replacement strategies in regenerative medicine.

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Generation of Induced Pluripotent Stem Cells from Human Cord Blood

Cited by 436 publications

References 14 publications

Generation of HLA-Universal iPSC-Derived Megakaryocytes and Platelets for Survival Under Refractoriness Conditions

Generation of HLA-Universal iPSC-Derived Megakaryocytes and Platelets for Survival Under Refractoriness Conditions

<b>Induction of neural crest cells from human dental pulp-derived induced pluripotent stem </b><b>cells </b>

A Novel Miniaturized Multimodal Bioreactor for Continuous In Situ Assessment of Bioartificial Cardiac Tissue During Stimulation and Maturation

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