vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint
statement of the International Federation for Adipose Therapeutics and Science (IFATS) and
the International So. Cytotherapy 15:641–648. https://doi.org/10.1016/j.jcyt.2013.02.006
37. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R,
Keating A, Prockop D, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.
Cytotherapy 8:315–317. https://doi.org/10.1080/14653240600855905
38. Cheng N-C, Chen S-Y, Li J-R, Young T-H (2013) Short-term spheroid formation enhances the
regenerative capacity of adipose-derived stem cells by promoting stemness, angiogenesis, and
chemotaxis. Stem Cells Transl Med 2:584–594. https://doi.org/10.5966/sctm.2013-0007
39. Bartosh TJ, Ylostalo JH, Mohammadipoor A, Bazhanov N, Coble K, Claypool K, Lee RH,
Choi H, Prockop DJ (2010) Aggregation of human mesenchymal stromal cells (MSCs) into
3D spheroids enhances their antiinflammatory properties. Proc Natl Acad Sci
107:13724–13729. https://doi.org/10.1073/pnas.1008117107
40. YlÖstalo JH, Bartosh TJ, Coble K, Prockop DJ (2012) Human mesenchymal stem/stromal
cells cultured as spheroids are self-activated to produce prostaglandin E2 that directs stimulated macrophages into an anti-inflammatory phenotype. Stem Cells 30:2283–2296. https://
doi.org/10.1002/stem.1191
41. Zimmermann JA, Mcdevitt TC (2014) Pre-conditioning mesenchymal stromal cell spheroids
for immunomodulatory paracrine factor secretion. Cytotherapy 16:331–345. https://doi.org/
10.1016/j.jcyt.2013.09.004
42. Horn P, Bokermann G, Cholewa D, Bork S, Walenda T, Koch C, Drescher W,
Hutschenreuther G, Zenke M, Ho AD, Wagner W (2010) Impact of individual platelet lysates
on isolation and growth of human mesenchymal stromal cells. Cytotherapy 12:888–898.
https://doi.org/10.3109/14653249.2010.501788
43. Badenes SM, Fernandes TG, Rodrigues CAV, Diogo MM, Cabral JMS (2016) Microcarrierbased platforms for in vitro expansion and differentiation of human pluripotent stem cells in
bioreactor culture systems. J Biotechnol 234:71–82. https://doi.org/10.1016/j.jbiotec.2016.07.
023
44. Villa-Diaz LG, Ross AM, Lahann J, Krebsbach PH (2013) Concise review: the evolution of
human pluripotent stem cell culture: from feeder cells to synthetic coatings. Stem Cells 31:1–7.
https://doi.org/10.1002/stem.1260
45. Shearier E, Xing Q, Qian Z, Zhao F (2016) Physiologically low oxygen enhances biomolecule
production and stemness of mesenchymal stem cell spheroids. Tissue Eng Part C Methods
22:360–369. https://doi.org/10.1089/ten.tec.2015.0465
46. Wu J, Rostami MR, Cadavid Olaya DP, Tzanakakis ES (2014) Oxygen transport and stem cell
aggregation in stirred-suspension bioreactor cultures. PLoS One 9:e102486. https://doi.org/10.
1371/journal.pone.0102486
47. Lei Y, Schaffer DV (2013) A fully defined and scalable 3D culture system for human
pluripotent stem cell expansion and differentiation. Proc Natl Acad Sci 110:E5039–E5048.
https://doi.org/10.1073/pnas.1309408110
48. Sart S, Tsai A-C, Li Y, Ma T (2014) Three-dimensional aggregates of mesenchymal stem
cells: cellular mechanisms, biological properties, and applications. Tissue Eng Part B Rev
20:365–380. https://doi.org/10.1089/ten.teb.2013.0537
49. Sucosky P, Osorio DF, Brown JB, Neitzel GP (2004) Fluid mechanics of a spinner-flask
bioreactor. Biotechnol Bioeng 85:34–46. https://doi.org/10.1002/bit.10788
50. Kaiser S, Jossen V, Schirmaier C, Eibl D, Brill S, van den Bos C, Eibl R (2013) Fluid flow and
cell proliferation of mesenchymal adipose-derived stem cells in small-scale, stirred, single-use
bioreactors. Chem Ing Tech 85:95–102. https://doi.org/10.1002/cite.201200180
51. vn Wezel AL (1967) Growth of cell-strains and primary cells on microcarriers in homogeneous culture. Nature 216:64–65
224
V. Jossen et al.
statement of the International Federation for Adipose Therapeutics and Science (IFATS) and
the International So. Cytotherapy 15:641–648. https://doi.org/10.1016/j.jcyt.2013.02.006
37. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R,
Keating A, Prockop D, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.
Cytotherapy 8:315–317. https://doi.org/10.1080/14653240600855905
38. Cheng N-C, Chen S-Y, Li J-R, Young T-H (2013) Short-term spheroid formation enhances the
regenerative capacity of adipose-derived stem cells by promoting stemness, angiogenesis, and
chemotaxis. Stem Cells Transl Med 2:584–594. https://doi.org/10.5966/sctm.2013-0007
39. Bartosh TJ, Ylostalo JH, Mohammadipoor A, Bazhanov N, Coble K, Claypool K, Lee RH,
Choi H, Prockop DJ (2010) Aggregation of human mesenchymal stromal cells (MSCs) into
3D spheroids enhances their antiinflammatory properties. Proc Natl Acad Sci
107:13724–13729. https://doi.org/10.1073/pnas.1008117107
40. YlÖstalo JH, Bartosh TJ, Coble K, Prockop DJ (2012) Human mesenchymal stem/stromal
cells cultured as spheroids are self-activated to produce prostaglandin E2 that directs stimulated macrophages into an anti-inflammatory phenotype. Stem Cells 30:2283–2296. https://
doi.org/10.1002/stem.1191
41. Zimmermann JA, Mcdevitt TC (2014) Pre-conditioning mesenchymal stromal cell spheroids
for immunomodulatory paracrine factor secretion. Cytotherapy 16:331–345. https://doi.org/
10.1016/j.jcyt.2013.09.004
42. Horn P, Bokermann G, Cholewa D, Bork S, Walenda T, Koch C, Drescher W,
Hutschenreuther G, Zenke M, Ho AD, Wagner W (2010) Impact of individual platelet lysates
on isolation and growth of human mesenchymal stromal cells. Cytotherapy 12:888–898.
https://doi.org/10.3109/14653249.2010.501788
43. Badenes SM, Fernandes TG, Rodrigues CAV, Diogo MM, Cabral JMS (2016) Microcarrierbased platforms for in vitro expansion and differentiation of human pluripotent stem cells in
bioreactor culture systems. J Biotechnol 234:71–82. https://doi.org/10.1016/j.jbiotec.2016.07.
023
44. Villa-Diaz LG, Ross AM, Lahann J, Krebsbach PH (2013) Concise review: the evolution of
human pluripotent stem cell culture: from feeder cells to synthetic coatings. Stem Cells 31:1–7.
https://doi.org/10.1002/stem.1260
45. Shearier E, Xing Q, Qian Z, Zhao F (2016) Physiologically low oxygen enhances biomolecule
production and stemness of mesenchymal stem cell spheroids. Tissue Eng Part C Methods
22:360–369. https://doi.org/10.1089/ten.tec.2015.0465
46. Wu J, Rostami MR, Cadavid Olaya DP, Tzanakakis ES (2014) Oxygen transport and stem cell
aggregation in stirred-suspension bioreactor cultures. PLoS One 9:e102486. https://doi.org/10.
1371/journal.pone.0102486
47. Lei Y, Schaffer DV (2013) A fully defined and scalable 3D culture system for human
pluripotent stem cell expansion and differentiation. Proc Natl Acad Sci 110:E5039–E5048.
https://doi.org/10.1073/pnas.1309408110
48. Sart S, Tsai A-C, Li Y, Ma T (2014) Three-dimensional aggregates of mesenchymal stem
cells: cellular mechanisms, biological properties, and applications. Tissue Eng Part B Rev
20:365–380. https://doi.org/10.1089/ten.teb.2013.0537
49. Sucosky P, Osorio DF, Brown JB, Neitzel GP (2004) Fluid mechanics of a spinner-flask
bioreactor. Biotechnol Bioeng 85:34–46. https://doi.org/10.1002/bit.10788
50. Kaiser S, Jossen V, Schirmaier C, Eibl D, Brill S, van den Bos C, Eibl R (2013) Fluid flow and
cell proliferation of mesenchymal adipose-derived stem cells in small-scale, stirred, single-use
bioreactors. Chem Ing Tech 85:95–102. https://doi.org/10.1002/cite.201200180
51. vn Wezel AL (1967) Growth of cell-strains and primary cells on microcarriers in homogeneous culture. Nature 216:64–65
224
V. Jossen et al.