18. Carter SM, Granchelli J, Stelzer T (2014) Large scale expansion and differentiation of human
mesenchymal stromal cells in the Thermo Scientific nunc cell factory system. Thermo Sci
Appl Note 1:1–6
19. Jossen V, Muoio F, Panella S, Harder Y, Tallone T, Eibl R (2020) An approach towards a
GMP compliant in-vitro expansion of human adipose stem cells for autologous therapies.
Bioengineering 7(3):77–100
20. Reichardt A, Polchow B, Shakibaei M, Henrich W, Hetzer R, Lueders C (2013) Large scale
expansion of human umbilical cord cells in a rotating bed system bioreactor for cardiovascular
tissue engineering applications. Open Biomed Eng J 7:50–61. https://doi.org/10.2174/
1874120701307010050
21. Ikebe C, Suzuki K (2014) Mesenchymal stem cells for regenerative therapy: optimization of
cell preparation protocols. Biomed Res Int 2014:1–11. https://doi.org/10.1155/2014/951512
22. Scibona E, Morbidelli M (2019) Expansion processes for cell-based therapies. Biotechnol Adv
37:107455. https://doi.org/10.1016/j.biotechadv.2019.107455
23. Discher DE, Mooney DJ, Zandstra PW (2010) Growth factors, matrices, and forces combine.
Growth (Lakeland) 324:1673–1677. https://doi.org/10.1126/science.1171643.Growth
24. Steward AJ, Kelly DJ (2015) Mechanical regulation of mesenchymal stem cell differentiation.
J Anat 227:717–731. https://doi.org/10.1111/joa.12243
25. Kaiser SC, Eibl D, Eibl R (2015) Single-use bioreactors for animal and human cells. In:
Animal cell culture: cell engineering. Springer, Cham, pp 445–499
26. Baraniak PR, McDevitt TC (2012) Scaffold-free culture of mesenchymal stem cell spheroids
in suspension preserves multilineage potential. Cell Tissue Res 347:701–711. https://doi.org/
10.1007/s00441-011-1215-5
27. Frith JE, Thomson B, Genever PG (2010) Dynamic three-dimensional culture methods
enhance mesenchymal stem cell properties and increase therapeutic potential. Tissue Eng
Part C Methods 16:735–749. https://doi.org/10.1089/ten.tec.2009.0432
28. Alimperti S, Lei P, Wen Y, Tian J, Campbell AM, Andreadis ST (2014) Serum-free spheroid
suspension culture maintains mesenchymal stem cell proliferation and differentiation potential. Biotechnol Prog 30:974–983. https://doi.org/10.1002/btpr.1904
29. Allen LM, Matyas J, Ungrin M, Hart DA, Sen A (2019) Serum-free culture of human
mesenchymal stem cell aggregates in suspension bioreactors for tissue engineering applications. Stem Cells Int 2019:1–18. https://doi.org/10.1155/2019/4607461
30. Bhang SH, Cho S-W, La W-G, Lee T-J, Yang HS, Sun A-Y, Baek S-H, Rhie J-W, Kim B-S
(2011) Angiogenesis in ischemic tissue produced by spheroid grafting of human adiposederived stromal cells. Biomaterials 32:2734–2747. https://doi.org/10.1016/j.biomaterials.
2010.12.035
31. Layer PG, Robitzki A, Rothermel A, Willbold E (2002) Of layers and spheres: the reaggregate
approach in tissue engineering. Trends Neurosci 25:131–134. https://doi.org/10.1016/S01662236(00)02036-1
32. Achilli T-M, Meyer J, Morgan JR (2012) Advances in the formation, use and understanding of
multi-cellular spheroids. Expert Opin Biol Ther 12:1347–1360. https://doi.org/10.1517/
14712598.2012.707181
33. Page H, Flood P, Reynaud EG (2013) Three-dimensional tissue cultures: current trends and
beyond. Cell Tissue Res 352:123–131. https://doi.org/10.1007/s00441-012-1441-5
34. Edmondson R, Broglie JJ, Adcock AF, Yang L (2014) Three-dimensional cell culture systems
and their applications in drug discovery and cell-based biosensors. Assay Drug Dev Technol
12:207–218. https://doi.org/10.1089/adt.2014.573
35. Caron MMJ, Emans PJ, Coolsen MME, Voss L, Surtel DAM, Cremers A, van Rhijn LW,
Welting TJM (2012) Redifferentiation of dedifferentiated human articular chondrocytes:
comparison of 2D and 3D cultures. Osteoarthr Cartil 20:1170–1178. https://doi.org/10.1016/
j.joca.2012.06.016
36. Bourin P, Bunnell BA, Casteilla L, Dominici M, Katz AJ, March KL, Redl H, Rubin JP,
Yoshimura K, Gimble JM (2013) Stromal cells from the adipose tissue-derived stromal
Numerical Methods for the Design and Description of In Vitro Expansion. . .
223
mesenchymal stromal cells in the Thermo Scientific nunc cell factory system. Thermo Sci
Appl Note 1:1–6
19. Jossen V, Muoio F, Panella S, Harder Y, Tallone T, Eibl R (2020) An approach towards a
GMP compliant in-vitro expansion of human adipose stem cells for autologous therapies.
Bioengineering 7(3):77–100
20. Reichardt A, Polchow B, Shakibaei M, Henrich W, Hetzer R, Lueders C (2013) Large scale
expansion of human umbilical cord cells in a rotating bed system bioreactor for cardiovascular
tissue engineering applications. Open Biomed Eng J 7:50–61. https://doi.org/10.2174/
1874120701307010050
21. Ikebe C, Suzuki K (2014) Mesenchymal stem cells for regenerative therapy: optimization of
cell preparation protocols. Biomed Res Int 2014:1–11. https://doi.org/10.1155/2014/951512
22. Scibona E, Morbidelli M (2019) Expansion processes for cell-based therapies. Biotechnol Adv
37:107455. https://doi.org/10.1016/j.biotechadv.2019.107455
23. Discher DE, Mooney DJ, Zandstra PW (2010) Growth factors, matrices, and forces combine.
Growth (Lakeland) 324:1673–1677. https://doi.org/10.1126/science.1171643.Growth
24. Steward AJ, Kelly DJ (2015) Mechanical regulation of mesenchymal stem cell differentiation.
J Anat 227:717–731. https://doi.org/10.1111/joa.12243
25. Kaiser SC, Eibl D, Eibl R (2015) Single-use bioreactors for animal and human cells. In:
Animal cell culture: cell engineering. Springer, Cham, pp 445–499
26. Baraniak PR, McDevitt TC (2012) Scaffold-free culture of mesenchymal stem cell spheroids
in suspension preserves multilineage potential. Cell Tissue Res 347:701–711. https://doi.org/
10.1007/s00441-011-1215-5
27. Frith JE, Thomson B, Genever PG (2010) Dynamic three-dimensional culture methods
enhance mesenchymal stem cell properties and increase therapeutic potential. Tissue Eng
Part C Methods 16:735–749. https://doi.org/10.1089/ten.tec.2009.0432
28. Alimperti S, Lei P, Wen Y, Tian J, Campbell AM, Andreadis ST (2014) Serum-free spheroid
suspension culture maintains mesenchymal stem cell proliferation and differentiation potential. Biotechnol Prog 30:974–983. https://doi.org/10.1002/btpr.1904
29. Allen LM, Matyas J, Ungrin M, Hart DA, Sen A (2019) Serum-free culture of human
mesenchymal stem cell aggregates in suspension bioreactors for tissue engineering applications. Stem Cells Int 2019:1–18. https://doi.org/10.1155/2019/4607461
30. Bhang SH, Cho S-W, La W-G, Lee T-J, Yang HS, Sun A-Y, Baek S-H, Rhie J-W, Kim B-S
(2011) Angiogenesis in ischemic tissue produced by spheroid grafting of human adiposederived stromal cells. Biomaterials 32:2734–2747. https://doi.org/10.1016/j.biomaterials.
2010.12.035
31. Layer PG, Robitzki A, Rothermel A, Willbold E (2002) Of layers and spheres: the reaggregate
approach in tissue engineering. Trends Neurosci 25:131–134. https://doi.org/10.1016/S01662236(00)02036-1
32. Achilli T-M, Meyer J, Morgan JR (2012) Advances in the formation, use and understanding of
multi-cellular spheroids. Expert Opin Biol Ther 12:1347–1360. https://doi.org/10.1517/
14712598.2012.707181
33. Page H, Flood P, Reynaud EG (2013) Three-dimensional tissue cultures: current trends and
beyond. Cell Tissue Res 352:123–131. https://doi.org/10.1007/s00441-012-1441-5
34. Edmondson R, Broglie JJ, Adcock AF, Yang L (2014) Three-dimensional cell culture systems
and their applications in drug discovery and cell-based biosensors. Assay Drug Dev Technol
12:207–218. https://doi.org/10.1089/adt.2014.573
35. Caron MMJ, Emans PJ, Coolsen MME, Voss L, Surtel DAM, Cremers A, van Rhijn LW,
Welting TJM (2012) Redifferentiation of dedifferentiated human articular chondrocytes:
comparison of 2D and 3D cultures. Osteoarthr Cartil 20:1170–1178. https://doi.org/10.1016/
j.joca.2012.06.016
36. Bourin P, Bunnell BA, Casteilla L, Dominici M, Katz AJ, March KL, Redl H, Rubin JP,
Yoshimura K, Gimble JM (2013) Stromal cells from the adipose tissue-derived stromal
Numerical Methods for the Design and Description of In Vitro Expansion. . .
223