Review Article

Three-Dimensional Bioreactor Technologies for the Cocultivation of Human Mesenchymal Stem/Stromal Cells and Beta Cells

Table 1

Process-relevant parameters for human mesenchymal stem/stromal cells (hMSCs) and islets or beta cells based on our own data and the literature.

hMSChMSC-TERTIslet1.1B4MIN6

Biological parameterμ [d−1]0.33–1.10.4–0.7#0.11 [49]0.840.19–0.23 [100]
tD [h]15–5024–421512072–88
qGLC [pmol cell−1 h−1]0.13–0.70.02–0.5#n.d.0.08#n.d.
qox [fmol cell−1 h−1]90–100 [77]300 [74]23–139 [89]n.d.

Process parameterSeeding density [cells cm−2]1000–10,000#Depends on reaggregation method5000–10,000#>80,000
Final cell density [cells cm−2]5·104 (dynamic)#
2·105 (static)#
1·105 (static)#2-3·105 (static)#
Max. working volume [L]352.4#<0.1
pH [−]7.0–7.4
T [°C]30–37
kLa [h−1]+0.64.40.2n.d.
Shear sensitivity τ [N cm−2]1.2·10−5Mostly static cultivation with low shear
Growth surface materialTC-treated polystyrene, micro- and macrocarrier with different coatingsMainly TC-treated culture vessels (polystyrene)
Aggregate formationPossible, but lower tendencyStrong tendency
Culture mediaSCM, SFM, CDMSCM with 10–20% serum
Glucose concentration [mM]Usually 5.5, 5–255.8 recommend, 5–25

Abbreviations: μ: growth rate; tD: doubling time; qGLC: glucose consumption; qox: oxygen consumption; kLa: oxygen transfer coefficient; TC: tissue culture; SCM: serum-containing medium; SFM: serum-free medium; CDM: chemically defined medium; n.d.: not determined. Murine origin; #own data; +aeration with air.