Investigation on the scale-up strategy and harvest for human mesenchymal stromal cell production in a dynamic bioreactor system: influences of medium, microcarrier choice and new harvest enzymes on the cell quality
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1. Verfasser: | |
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Format: | Abschlussarbeit Buch |
Sprache: | English |
Veröffentlicht: |
Düren
Shaker Verlag
2019
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Schriftenreihe: | Schriftenreihe des Institutes für Bioverfahrenstechnik und Pharmazeutische Technologie
Band 13 |
Schlagworte: | |
Online-Zugang: | Inhaltsverzeichnis Inhaltsverzeichnis |
Beschreibung: | XVIII, 112 Seiten Illustrationen, Diagramme 21 cm, 185 g |
ISBN: | 9783844068580 3844068589 |
Internformat
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100 | 1 | |a Leber, Jasmin |e Verfasser |0 (DE-588)1193586275 |4 aut | |
245 | 1 | 0 | |a Investigation on the scale-up strategy and harvest for human mesenchymal stromal cell production in a dynamic bioreactor system |b influences of medium, microcarrier choice and new harvest enzymes on the cell quality |c Jasmin Leber |
264 | 1 | |a Düren |b Shaker Verlag |c 2019 | |
300 | |a XVIII, 112 Seiten |b Illustrationen, Diagramme |c 21 cm, 185 g | ||
336 | |b txt |2 rdacontent | ||
337 | |b n |2 rdamedia | ||
338 | |b nc |2 rdacarrier | ||
490 | 1 | |a Schriftenreihe des Institutes für Bioverfahrenstechnik und Pharmazeutische Technologie |v Band 13 | |
502 | |b Dissertation |c Justus-Liebig-Universität Gießen |d 2019 | ||
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650 | 0 | 7 | |a Festbettreaktor |0 (DE-588)4113549-0 |2 gnd |9 rswk-swf |
650 | 0 | 7 | |a Reaktionstechnik |0 (DE-588)4136173-8 |2 gnd |9 rswk-swf |
650 | 0 | 7 | |a Zellkultur |0 (DE-588)4067547-6 |2 gnd |9 rswk-swf |
650 | 0 | 7 | |a Mesenchymzelle |0 (DE-588)4278308-2 |2 gnd |9 rswk-swf |
650 | 0 | 7 | |a Maßstabübertragung |0 (DE-588)4279219-8 |2 gnd |9 rswk-swf |
653 | |a Advanced Therapy Medicinal Products | ||
653 | |a bead-to-bead transfer | ||
653 | |a cell harvest | ||
653 | |a chemically defined medium | ||
653 | |a hMSC-TERT | ||
653 | |a mesenchymal stem/stromal cells | ||
653 | |a microcarriers | ||
653 | |a proteases | ||
653 | |a scale-up | ||
653 | |a stirred tank bioreactor | ||
655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
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Datensatz im Suchindex
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---|---|
adam_text | VII
INHALT
ABSTRACT
.........................................................................................................
ILL
ZUSAMMENFASSUNG
..........................................................................................V
PUBLICATIONS
AND
CONFERENCE
PROCEEDINGS
................................................ XI
GLOSSARY
........................................................................................................
XV
1.
INTRODUCTION
................................................................................................
1
1.1.
OBJECTIVE
................................................................................................
1
1.2.
CELL
THERAPY
............................................................................................
3
1.3.
HUMAN
MESENCHYMAL
STROMAL
CELL
PRODUCTION
..................................
6
1.3.1.
EXPANSION
SYSTEMS
.....................................................................
6
1.3.2.
CELL
ATTACHMENT
..........................................................................
6
1.3.3.
MICROCARRIERS
.............................................................................
7
1.3.4.
CULTURE
MEDIUM
..........................
..............................................
8
1.3.5.
CELL
HARVEST
..............................................................................
12
1.3.6.
DOWNSTREAM
PROCESSING
..........................................................
13
1.4.
CELL
SOURCES
AND
DONOR
VARIABILITY
.....................................................
14
1.5.
HUMAN
MESENCHYMAL
STROMAL
CELL
QUALITY
CONTROL
..........................
15
1.5.1.
MINIMAL
CRITERIA
FOR
RESEARCH
PURPOSES
...................................
15
1.5.2.
CRITERIA
FOR
CLINICAL
APPLICATIONS
.............................................
17
1.5.3.
CELL
STRESS
.................................................................................
19
2.
MATERIALS
AND
METHODS
............................................................................
21
2.1.
CELL
CULTURE
METHODS
...........................................................................
21
2.1.1.
MEDIA
AND
SUPPLEMENTS
..........................................................
21
2.1.2.
CELLS
.........................................................................................
21
2.1.3.
STATIC
CULTURES
IN
TISSUE
FLASKS
.................................................
22
2.1.4.
CELL
ATTACHMENT
AND
SPREADING
QUANTIFICATION
........................
22
2.1.5.
MICROCARRIERS
...........................................................................
23
2.1.6.
SPINNER
CULTURES
.......................................................................
24
2.1.7.
BEAD-TO-BEAD
TRANSFER
IN
SPINNER
FLASKS
.................................
24
2.1.8.
BIOREACTOR
EXPANSION
..........................
25
2.1.9.
DIFFERENTIATION
.........................................................................
26
VIII
CONTENT
2.2.
HARVEST
METHODS
..................................................................................
26
2.2.1.
ENZYMES
FROM
NEW
SOURCES
....................................................
26
2.2.2.
CELL
DETACHMENT
IN
STATIC
CULTURES
...........................................
27
2.2.3.
HARVEST
OF
DISSOLVABLE
MICROCARRIERS
.....................................
27
2.2.4.
HARVEST
OF
BIOREACTOR
WITH
BOTTOM
DRAIN
..............................
27
2.2.5.
HARVEST
OF
BIOREACTOR
WITH
EXTERNAL
FILTER
.............................
28
2.3.
ANALYTICAL
METHODS
............................................................................
28
2.3.1.
CELL
COUNT
DETERMINATION
FROM
MICROCARRIERS
.......................
29
2.3.2.
STAINING
OF
ADHERENT
CELLS
.......................................................
29
2.3.3.
STAINING
OF
MICROCARRIERS
WITH
RHODAMINE
............................. 29
2.3.4.
METABOLIC
ANALYSIS
OF
CELL
CULTURE
MEDIA
..............................
30
2.3.5.
DETECTION
OF
DIFFERENTIATED
CELLS
............................................
30
2.3.6.
SURFACE
MARKER
ANALYSIS
USING
FLOW
CYTOMETRY
.....................
30
2.3.7.
GENE
EXPRESSION
ANALYSIS
BY
QPCR
........................................
31
2.3.8.
IN
SILICO
ANALYSIS
......................................................................
31
2.4.
CALCULATIONS
AND
DATA
PRESENTATION
....................................................
32
3.
ANALYSIS
OF
PROCESS
PARAMETERS
............................................................. 35
3.1.
MIXING
..................................................................................................
35
3.1.1.
MINIMAL
POWER
INPUT
..................................................
35
3.1.2.
MAXIMAL
STIRRING
RATE
TO
AVOID
CELL
STRESS
..............................
39
3.2.
OXYGEN
TRANSFER
............................................................................
40
3.2.1.
OXYGEN
DEMAND
OF
HMSC
......................................................
40
3.2.2.
BIOENGINEERING
FACTORS
THAT
INFLUENCE
THE
OXYGEN
SUPPLY
....41
3.3.
SCALE-UP
................................................................................................
43
4.
RESULTS
........................................................................................................
45
4.1.
ESTABLISHMENT
OF
A
DEFINED
EXPANSION
ENVIRONMENT
.........................
45
4.1.1.
CULTURE
OF
HMSC-TERT
IN
SERUM-CONTAINING
MEDIUM
......
45
4.1.2.
CULTURE
OF
HMSC-TERT
IN
HPL-CONTAINING
MEDIUM
...........
49
4.1.3.
CULTURE
OF
HMSC-TERT
IN
CHEMICALLY
DEFINED
MEDIUM
....
52
4.2.
PROCESS
TRANSFER
FOR
PRIMARY
HMSC
...................................................
56
4.2.1.
CULTURE
OF
BM-HMSC
IN
SERUM-CONTAINING
MEDIUM
...........
57
4.2.2.
CULTURE
OF
BM-HMSC
IN
CHEMICALLY
DEFINED
MEDIUM
..........
58
IX
4.3.
HARVEST
OF
HMSC
................................................................................
61
4.3.1.
ALTERNATIVE
ENZYMES
FOR
CELL
DETACHMENT
..............................
61
4.3.2.
HARVEST
OF
HMSC
FROM
MICROCARRIERS
....................................
65
4.4.
QUALITY
CONTROL
....................................................................................
68
4.4.1.
SURFACE
MARKERS
.......................................................................
68
4.4.2.
DIFFERENTIABILITY
.......................................................................
70
4.4.3.
CELL
STRESS
.................................................................................
72
5.
DISCUSSION
..................................................................................................
75
5.1.
DEFINED
MEDIUM
IN
THE
UPSTREAM
PROCESSING:
ONE
SOLUTION
FOR
EVERY
SCALE
OF
HMSC
EXPANSION?
.................................................................
75
5.2.
CELLS
AS
THE
PRODUCT:
HARVEST
AS
RESTRICTING
PROCESS
STEP
...................
80
5.3.
WHAT
ARE
QUALITY
ATTRIBUTES
FOR
A
CELL
THERAPY
PRODUCT?
.....................
82
5.4.
CONCLUSION
...........................................................................................
84
6.
OUTLOOK
......................................................................................................
85
7.
REFERENCES
.................................................................................................
87
8.
APPENDIX
.................................................................................................
101
8.1.
GENE-EXPRESSION
BASED
CELL
STRESS
ANALYSIS
......................................
101
8.2.
LIST
OF
FIGURES
.....................................................................................
106
8.3.
LIST
OF
TABLES
.......................................................................................
110
DANKSAGUNG
..................................................................................................
ILL
|
adam_txt |
VII
INHALT
ABSTRACT
.
ILL
ZUSAMMENFASSUNG
.V
PUBLICATIONS
AND
CONFERENCE
PROCEEDINGS
. XI
GLOSSARY
.
XV
1.
INTRODUCTION
.
1
1.1.
OBJECTIVE
.
1
1.2.
CELL
THERAPY
.
3
1.3.
HUMAN
MESENCHYMAL
STROMAL
CELL
PRODUCTION
.
6
1.3.1.
EXPANSION
SYSTEMS
.
6
1.3.2.
CELL
ATTACHMENT
.
6
1.3.3.
MICROCARRIERS
.
7
1.3.4.
CULTURE
MEDIUM
.
.
8
1.3.5.
CELL
HARVEST
.
12
1.3.6.
DOWNSTREAM
PROCESSING
.
13
1.4.
CELL
SOURCES
AND
DONOR
VARIABILITY
.
14
1.5.
HUMAN
MESENCHYMAL
STROMAL
CELL
QUALITY
CONTROL
.
15
1.5.1.
MINIMAL
CRITERIA
FOR
RESEARCH
PURPOSES
.
15
1.5.2.
CRITERIA
FOR
CLINICAL
APPLICATIONS
.
17
1.5.3.
CELL
STRESS
.
19
2.
MATERIALS
AND
METHODS
.
21
2.1.
CELL
CULTURE
METHODS
.
21
2.1.1.
MEDIA
AND
SUPPLEMENTS
.
21
2.1.2.
CELLS
.
21
2.1.3.
STATIC
CULTURES
IN
TISSUE
FLASKS
.
22
2.1.4.
CELL
ATTACHMENT
AND
SPREADING
QUANTIFICATION
.
22
2.1.5.
MICROCARRIERS
.
23
2.1.6.
SPINNER
CULTURES
.
24
2.1.7.
BEAD-TO-BEAD
TRANSFER
IN
SPINNER
FLASKS
.
24
2.1.8.
BIOREACTOR
EXPANSION
.
25
2.1.9.
DIFFERENTIATION
.
26
VIII
CONTENT
2.2.
HARVEST
METHODS
.
26
2.2.1.
ENZYMES
FROM
NEW
SOURCES
.
26
2.2.2.
CELL
DETACHMENT
IN
STATIC
CULTURES
.
27
2.2.3.
HARVEST
OF
DISSOLVABLE
MICROCARRIERS
.
27
2.2.4.
HARVEST
OF
BIOREACTOR
WITH
BOTTOM
DRAIN
.
27
2.2.5.
HARVEST
OF
BIOREACTOR
WITH
EXTERNAL
FILTER
.
28
2.3.
ANALYTICAL
METHODS
.
28
2.3.1.
CELL
COUNT
DETERMINATION
FROM
MICROCARRIERS
.
29
2.3.2.
STAINING
OF
ADHERENT
CELLS
.
29
2.3.3.
STAINING
OF
MICROCARRIERS
WITH
RHODAMINE
. 29
2.3.4.
METABOLIC
ANALYSIS
OF
CELL
CULTURE
MEDIA
.
30
2.3.5.
DETECTION
OF
DIFFERENTIATED
CELLS
.
30
2.3.6.
SURFACE
MARKER
ANALYSIS
USING
FLOW
CYTOMETRY
.
30
2.3.7.
GENE
EXPRESSION
ANALYSIS
BY
QPCR
.
31
2.3.8.
IN
SILICO
ANALYSIS
.
31
2.4.
CALCULATIONS
AND
DATA
PRESENTATION
.
32
3.
ANALYSIS
OF
PROCESS
PARAMETERS
. 35
3.1.
MIXING
.
35
3.1.1.
MINIMAL
POWER
INPUT
.
35
3.1.2.
MAXIMAL
STIRRING
RATE
TO
AVOID
CELL
STRESS
.
39
3.2.
OXYGEN
TRANSFER
.
40
3.2.1.
OXYGEN
DEMAND
OF
HMSC
.
40
3.2.2.
BIOENGINEERING
FACTORS
THAT
INFLUENCE
THE
OXYGEN
SUPPLY
.41
3.3.
SCALE-UP
.
43
4.
RESULTS
.
45
4.1.
ESTABLISHMENT
OF
A
DEFINED
EXPANSION
ENVIRONMENT
.
45
4.1.1.
CULTURE
OF
HMSC-TERT
IN
SERUM-CONTAINING
MEDIUM
.
45
4.1.2.
CULTURE
OF
HMSC-TERT
IN
HPL-CONTAINING
MEDIUM
.
49
4.1.3.
CULTURE
OF
HMSC-TERT
IN
CHEMICALLY
DEFINED
MEDIUM
.
52
4.2.
PROCESS
TRANSFER
FOR
PRIMARY
HMSC
.
56
4.2.1.
CULTURE
OF
BM-HMSC
IN
SERUM-CONTAINING
MEDIUM
.
57
4.2.2.
CULTURE
OF
BM-HMSC
IN
CHEMICALLY
DEFINED
MEDIUM
.
58
IX
4.3.
HARVEST
OF
HMSC
.
61
4.3.1.
ALTERNATIVE
ENZYMES
FOR
CELL
DETACHMENT
.
61
4.3.2.
HARVEST
OF
HMSC
FROM
MICROCARRIERS
.
65
4.4.
QUALITY
CONTROL
.
68
4.4.1.
SURFACE
MARKERS
.
68
4.4.2.
DIFFERENTIABILITY
.
70
4.4.3.
CELL
STRESS
.
72
5.
DISCUSSION
.
75
5.1.
DEFINED
MEDIUM
IN
THE
UPSTREAM
PROCESSING:
ONE
SOLUTION
FOR
EVERY
SCALE
OF
HMSC
EXPANSION?
.
75
5.2.
CELLS
AS
THE
PRODUCT:
HARVEST
AS
RESTRICTING
PROCESS
STEP
.
80
5.3.
WHAT
ARE
QUALITY
ATTRIBUTES
FOR
A
CELL
THERAPY
PRODUCT?
.
82
5.4.
CONCLUSION
.
84
6.
OUTLOOK
.
85
7.
REFERENCES
.
87
8.
APPENDIX
.
101
8.1.
GENE-EXPRESSION
BASED
CELL
STRESS
ANALYSIS
.
101
8.2.
LIST
OF
FIGURES
.
106
8.3.
LIST
OF
TABLES
.
110
DANKSAGUNG
.
ILL |
any_adam_object | 1 |
any_adam_object_boolean | 1 |
author | Leber, Jasmin |
author_GND | (DE-588)1193586275 |
author_facet | Leber, Jasmin |
author_role | aut |
author_sort | Leber, Jasmin |
author_variant | j l jl |
building | Verbundindex |
bvnumber | BV048388321 |
classification_rvk | WF 9725 |
ctrlnum | (OCoLC)1110047589 (DE-599)DNB1190976420 |
dewey-full | 660.63 681.761 |
dewey-hundreds | 600 - Technology (Applied sciences) |
dewey-ones | 660 - Chemical engineering 681 - Precision instruments and other devices |
dewey-raw | 660.63 681.761 |
dewey-search | 660.63 681.761 |
dewey-sort | 3660.63 |
dewey-tens | 660 - Chemical engineering 680 - Manufacture of products for specific uses |
discipline | Chemie / Pharmazie Handwerk und Gewerbe / Verschiedene Technologien Biologie |
discipline_str_mv | Chemie / Pharmazie Handwerk und Gewerbe / Verschiedene Technologien Biologie |
format | Thesis Book |
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genre | (DE-588)4113937-9 Hochschulschrift gnd-content |
genre_facet | Hochschulschrift |
id | DE-604.BV048388321 |
illustrated | Illustrated |
index_date | 2024-07-03T20:20:20Z |
indexdate | 2024-07-10T09:36:44Z |
institution | BVB |
institution_GND | (DE-588)1064118135 |
isbn | 9783844068580 3844068589 |
language | English |
oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-033767074 |
oclc_num | 1110047589 |
open_access_boolean | |
owner | DE-355 DE-BY-UBR |
owner_facet | DE-355 DE-BY-UBR |
physical | XVIII, 112 Seiten Illustrationen, Diagramme 21 cm, 185 g |
publishDate | 2019 |
publishDateSearch | 2019 |
publishDateSort | 2019 |
publisher | Shaker Verlag |
record_format | marc |
series | Schriftenreihe des Institutes für Bioverfahrenstechnik und Pharmazeutische Technologie |
series2 | Schriftenreihe des Institutes für Bioverfahrenstechnik und Pharmazeutische Technologie |
spelling | Leber, Jasmin Verfasser (DE-588)1193586275 aut Investigation on the scale-up strategy and harvest for human mesenchymal stromal cell production in a dynamic bioreactor system influences of medium, microcarrier choice and new harvest enzymes on the cell quality Jasmin Leber Düren Shaker Verlag 2019 XVIII, 112 Seiten Illustrationen, Diagramme 21 cm, 185 g txt rdacontent n rdamedia nc rdacarrier Schriftenreihe des Institutes für Bioverfahrenstechnik und Pharmazeutische Technologie Band 13 Dissertation Justus-Liebig-Universität Gießen 2019 Rührreaktor (DE-588)4115803-9 gnd rswk-swf Festbettreaktor (DE-588)4113549-0 gnd rswk-swf Reaktionstechnik (DE-588)4136173-8 gnd rswk-swf Zellkultur (DE-588)4067547-6 gnd rswk-swf Mesenchymzelle (DE-588)4278308-2 gnd rswk-swf Maßstabübertragung (DE-588)4279219-8 gnd rswk-swf Advanced Therapy Medicinal Products bead-to-bead transfer cell harvest chemically defined medium hMSC-TERT mesenchymal stem/stromal cells microcarriers proteases scale-up stirred tank bioreactor (DE-588)4113937-9 Hochschulschrift gnd-content Mesenchymzelle (DE-588)4278308-2 s Zellkultur (DE-588)4067547-6 s Festbettreaktor (DE-588)4113549-0 s Rührreaktor (DE-588)4115803-9 s Reaktionstechnik (DE-588)4136173-8 s Maßstabübertragung (DE-588)4279219-8 s DE-604 Shaker Verlag (DE-588)1064118135 pbl Schriftenreihe des Institutes für Bioverfahrenstechnik und Pharmazeutische Technologie Band 13 (DE-604)BV042201309 13 B:DE-101 application/pdf https://d-nb.info/1190976420/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=033767074&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
spellingShingle | Leber, Jasmin Investigation on the scale-up strategy and harvest for human mesenchymal stromal cell production in a dynamic bioreactor system influences of medium, microcarrier choice and new harvest enzymes on the cell quality Schriftenreihe des Institutes für Bioverfahrenstechnik und Pharmazeutische Technologie Rührreaktor (DE-588)4115803-9 gnd Festbettreaktor (DE-588)4113549-0 gnd Reaktionstechnik (DE-588)4136173-8 gnd Zellkultur (DE-588)4067547-6 gnd Mesenchymzelle (DE-588)4278308-2 gnd Maßstabübertragung (DE-588)4279219-8 gnd |
subject_GND | (DE-588)4115803-9 (DE-588)4113549-0 (DE-588)4136173-8 (DE-588)4067547-6 (DE-588)4278308-2 (DE-588)4279219-8 (DE-588)4113937-9 |
title | Investigation on the scale-up strategy and harvest for human mesenchymal stromal cell production in a dynamic bioreactor system influences of medium, microcarrier choice and new harvest enzymes on the cell quality |
title_auth | Investigation on the scale-up strategy and harvest for human mesenchymal stromal cell production in a dynamic bioreactor system influences of medium, microcarrier choice and new harvest enzymes on the cell quality |
title_exact_search | Investigation on the scale-up strategy and harvest for human mesenchymal stromal cell production in a dynamic bioreactor system influences of medium, microcarrier choice and new harvest enzymes on the cell quality |
title_exact_search_txtP | Investigation on the scale-up strategy and harvest for human mesenchymal stromal cell production in a dynamic bioreactor system influences of medium, microcarrier choice and new harvest enzymes on the cell quality |
title_full | Investigation on the scale-up strategy and harvest for human mesenchymal stromal cell production in a dynamic bioreactor system influences of medium, microcarrier choice and new harvest enzymes on the cell quality Jasmin Leber |
title_fullStr | Investigation on the scale-up strategy and harvest for human mesenchymal stromal cell production in a dynamic bioreactor system influences of medium, microcarrier choice and new harvest enzymes on the cell quality Jasmin Leber |
title_full_unstemmed | Investigation on the scale-up strategy and harvest for human mesenchymal stromal cell production in a dynamic bioreactor system influences of medium, microcarrier choice and new harvest enzymes on the cell quality Jasmin Leber |
title_short | Investigation on the scale-up strategy and harvest for human mesenchymal stromal cell production in a dynamic bioreactor system |
title_sort | investigation on the scale up strategy and harvest for human mesenchymal stromal cell production in a dynamic bioreactor system influences of medium microcarrier choice and new harvest enzymes on the cell quality |
title_sub | influences of medium, microcarrier choice and new harvest enzymes on the cell quality |
topic | Rührreaktor (DE-588)4115803-9 gnd Festbettreaktor (DE-588)4113549-0 gnd Reaktionstechnik (DE-588)4136173-8 gnd Zellkultur (DE-588)4067547-6 gnd Mesenchymzelle (DE-588)4278308-2 gnd Maßstabübertragung (DE-588)4279219-8 gnd |
topic_facet | Rührreaktor Festbettreaktor Reaktionstechnik Zellkultur Mesenchymzelle Maßstabübertragung Hochschulschrift |
url | https://d-nb.info/1190976420/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=033767074&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
volume_link | (DE-604)BV042201309 |
work_keys_str_mv | AT leberjasmin investigationonthescaleupstrategyandharvestforhumanmesenchymalstromalcellproductioninadynamicbioreactorsysteminfluencesofmediummicrocarrierchoiceandnewharvestenzymesonthecellquality AT shakerverlag investigationonthescaleupstrategyandharvestforhumanmesenchymalstromalcellproductioninadynamicbioreactorsysteminfluencesofmediummicrocarrierchoiceandnewharvestenzymesonthecellquality |
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