Good Manufacturing Practice–compliant human induced pluripotent stem cells: from bench to putative clinical products
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Good Manufacturing Practice–compliant human induced pluripotent stem cells : from bench to putative clinical products. / Novoa, Juan J.; Westra, Inge M.; Steeneveld, Esther; Fonseca Neves, Natascha; Arendzen, Christiaan H.; Rajaei, Bahareh; Grundeken, Esmée; Yildiz, Mehmet; van der Valk, Wouter; Salvador, Alison; Carlotti, Françoise; Dijkers, Pascale F.; Locher, Heiko; van den Berg, Cathelijne W.; Raymond, Karine I.; Kirkeby, Agnete; Mummery, Christine L.; Rabelink, Ton J.; Freund, Christian; Meij, Pauline; Wieles, Brigitte.
In: Cytotherapy, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Good Manufacturing Practice–compliant human induced pluripotent stem cells
T2 - from bench to putative clinical products
AU - Novoa, Juan J.
AU - Westra, Inge M.
AU - Steeneveld, Esther
AU - Fonseca Neves, Natascha
AU - Arendzen, Christiaan H.
AU - Rajaei, Bahareh
AU - Grundeken, Esmée
AU - Yildiz, Mehmet
AU - van der Valk, Wouter
AU - Salvador, Alison
AU - Carlotti, Françoise
AU - Dijkers, Pascale F.
AU - Locher, Heiko
AU - van den Berg, Cathelijne W.
AU - Raymond, Karine I.
AU - Kirkeby, Agnete
AU - Mummery, Christine L.
AU - Rabelink, Ton J.
AU - Freund, Christian
AU - Meij, Pauline
AU - Wieles, Brigitte
N1 - Publisher Copyright: © 2024 International Society for Cell & Gene Therapy
PY - 2024
Y1 - 2024
N2 - Background aims: Few human induced pluripotent stem cell (hiPSC) lines are Good Manufacturing Practice (GMP)-compliant, limiting the clinical use of hiPSC-derived products. Here, we addressed this by establishing and validating an in-house platform to produce GMP-compliant hiPSCs that would be appropriate for producing both allogeneic and autologous hiPSC-derived products. Methods: Our standard research protocol for hiPSCs production was adapted and translated into a GMP-compliant platform. In addition to the generation of GMP-compliant hiPSC, the platform entails the methodology for donor recruitment, consent and screening, donor material procurement, hiPSCs manufacture, in-process control, specific QC test validation, QC testing, product release, hiPSCs storage and stability testing. For platform validation, one test run and three production runs were performed. Highest-quality lines were selected to establish master cell banks (MCBs). Results: Two MCBs were successfully released under GMP conditions. They demonstrated safety (sterility, negative mycoplasma, endotoxins <5.0 EU/mL and negative adventitious agents), cell identity (>75% of cells expressing markers of undifferentiated state, identical STR profile, normal karyotype in >20 metaphases), purity (negative residual vectors and no plasmid integration in the genome) and potency (expression of at least two of the three markers for each of the three germ layers). In addition, directed differentiation to somitoids (skeletal muscle precursors) and six potential clinical products from all three germ layers was achieved: pancreatic islets (endoderm), kidney organoids and cardiomyocytes (mesoderm), and keratinocytes, GABAergic interneurons and inner-ear organoids (ectoderm). Conclusions: We successfully developed and validated a platform for generating GMP-compliant hiPSC lines. The two MCBs released were shown to differentiate into clinical products relevant for our own and other regenerative medicine interests.
AB - Background aims: Few human induced pluripotent stem cell (hiPSC) lines are Good Manufacturing Practice (GMP)-compliant, limiting the clinical use of hiPSC-derived products. Here, we addressed this by establishing and validating an in-house platform to produce GMP-compliant hiPSCs that would be appropriate for producing both allogeneic and autologous hiPSC-derived products. Methods: Our standard research protocol for hiPSCs production was adapted and translated into a GMP-compliant platform. In addition to the generation of GMP-compliant hiPSC, the platform entails the methodology for donor recruitment, consent and screening, donor material procurement, hiPSCs manufacture, in-process control, specific QC test validation, QC testing, product release, hiPSCs storage and stability testing. For platform validation, one test run and three production runs were performed. Highest-quality lines were selected to establish master cell banks (MCBs). Results: Two MCBs were successfully released under GMP conditions. They demonstrated safety (sterility, negative mycoplasma, endotoxins <5.0 EU/mL and negative adventitious agents), cell identity (>75% of cells expressing markers of undifferentiated state, identical STR profile, normal karyotype in >20 metaphases), purity (negative residual vectors and no plasmid integration in the genome) and potency (expression of at least two of the three markers for each of the three germ layers). In addition, directed differentiation to somitoids (skeletal muscle precursors) and six potential clinical products from all three germ layers was achieved: pancreatic islets (endoderm), kidney organoids and cardiomyocytes (mesoderm), and keratinocytes, GABAergic interneurons and inner-ear organoids (ectoderm). Conclusions: We successfully developed and validated a platform for generating GMP-compliant hiPSC lines. The two MCBs released were shown to differentiate into clinical products relevant for our own and other regenerative medicine interests.
KW - cell therapy
KW - GMP production
KW - hiPSC-derived products
KW - human induced pluripotent stem cells
KW - quality control testing
U2 - 10.1016/j.jcyt.2024.02.021
DO - 10.1016/j.jcyt.2024.02.021
M3 - Journal article
C2 - 38483359
AN - SCOPUS:85187992275
JO - Cytotherapy
JF - Cytotherapy
SN - 1465-3249
ER -
ID: 387269617