Identification of critical process parameters for expansion of clinical grade human Wharton's jelly-derived mesenchymal stromal cells in stirred-tank bioreactors
© 2024 Wiley-VCH GmbH..
Cell therapies based on multipotent mesenchymal stromal cells (MSCs) are traditionally produced using 2D culture systems and platelet lysate- or serum-containing media (SCM). Although cost-effective for single-dose autologous treatments, this approach is not suitable for larger scale manufacturing (e.g., multiple-dose autologous or allogeneic therapies with banked MSCs); automated, scalable and Good Manufacturing Practices (GMP)-compliant platforms are urgently needed. The feasibility of transitioning was evaluated from an established Wharton's jelly MSCs (WJ-MSCs) 2D production strategy to a new one with stirred-tank bioreactors (STRs). Experimental conditions included four GMP-compliant xeno- and serum-free media (XSFM) screened in 2D conditions and two GMP-grade microcarriers assessed in 0.25 L-STRs using SCM. From the screening, a XSFM was selected and compared against SCM using the best-performing microcarrier. It was observed that SCM outperformed the 2D-selected medium in STRs, reinforcing the importance of 2D-to-3D transition studies before translation into clinical production settings. It was also found that attachment efficiency and microcarrier colonization were essential to attain higher fold expansions, and were therefore defined as critical process parameters. Nevertheless, WJ-MSCs were readily expanded in STRs with both media, preserving critical quality attributes in terms of identity, viability and differentiation potency, and yielding up to 1.47 × 109 cells in a real-scale 2.4-L batch.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:19 |
|---|---|
| Enthalten in: |
Biotechnology journal - 19(2024), 2 vom: 20. Feb., Seite e2300381 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
López-Fernández, Alba [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 27.02.2024 Date Revised 27.02.2024 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1002/biot.202300381 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM368934373 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM368934373 | ||
| 003 | DE-627 | ||
| 005 | 20240229164853.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240229s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/biot.202300381 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1309.xml |
| 035 | |a (DE-627)NLM368934373 | ||
| 035 | |a (NLM)38403461 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a López-Fernández, Alba |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Identification of critical process parameters for expansion of clinical grade human Wharton's jelly-derived mesenchymal stromal cells in stirred-tank bioreactors |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 27.02.2024 | ||
| 500 | |a Date Revised 27.02.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024 Wiley-VCH GmbH. | ||
| 520 | |a Cell therapies based on multipotent mesenchymal stromal cells (MSCs) are traditionally produced using 2D culture systems and platelet lysate- or serum-containing media (SCM). Although cost-effective for single-dose autologous treatments, this approach is not suitable for larger scale manufacturing (e.g., multiple-dose autologous or allogeneic therapies with banked MSCs); automated, scalable and Good Manufacturing Practices (GMP)-compliant platforms are urgently needed. The feasibility of transitioning was evaluated from an established Wharton's jelly MSCs (WJ-MSCs) 2D production strategy to a new one with stirred-tank bioreactors (STRs). Experimental conditions included four GMP-compliant xeno- and serum-free media (XSFM) screened in 2D conditions and two GMP-grade microcarriers assessed in 0.25 L-STRs using SCM. From the screening, a XSFM was selected and compared against SCM using the best-performing microcarrier. It was observed that SCM outperformed the 2D-selected medium in STRs, reinforcing the importance of 2D-to-3D transition studies before translation into clinical production settings. It was also found that attachment efficiency and microcarrier colonization were essential to attain higher fold expansions, and were therefore defined as critical process parameters. Nevertheless, WJ-MSCs were readily expanded in STRs with both media, preserving critical quality attributes in terms of identity, viability and differentiation potency, and yielding up to 1.47 × 109 cells in a real-scale 2.4-L batch | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a GMP-compliant scale-up | |
| 650 | 4 | |a critical process parameters | |
| 650 | 4 | |a human Wharton's jelly-derived mesenchymal stromal cells | |
| 650 | 4 | |a microcarriers | |
| 650 | 4 | |a stirred-tank bioreactors | |
| 650 | 4 | |a xeno- and serum-free media | |
| 650 | 7 | |a Culture Media, Serum-Free |2 NLM | |
| 700 | 1 | |a Garcia-Gragera, Víctor |e verfasserin |4 aut | |
| 700 | 1 | |a Lecina, Martí |e verfasserin |4 aut | |
| 700 | 1 | |a Vives, Joaquim |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Biotechnology journal |d 2006 |g 19(2024), 2 vom: 20. Feb., Seite e2300381 |w (DE-627)NLM164618910 |x 1860-7314 |7 nnns |
| 773 | 1 | 8 | |g volume:19 |g year:2024 |g number:2 |g day:20 |g month:02 |g pages:e2300381 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1002/biot.202300381 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 19 |j 2024 |e 2 |b 20 |c 02 |h e2300381 | ||