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. Author manuscript; available in PMC: 2023 Jan 1.
Published in final edited form as: Nat Biomed Eng. 2021 Jun 3;6(1):54–66. doi: 10.1038/s41551-021-00740-x

Fig. 5 |. Deterministic model predicts the effect of gel-coated MSCs on lung tissue collagen levels in different stages of bleomycin-induced injury.

Fig. 5 |

a, Schematic depicting model of cell therapy to control host tissue collagen by delivering soluble interstitial collagenases (Supplementary Text). αMSC is the clearance rate of donor MSCs. βmmp (maximum production rate) and θtnf-α (dose response of TNF-α) determine collagenase production by MSCs. Bleomycin (bleo) induces collagen production at the rate βcol, while collagenases degrade collagen based on the Michaelis–Menten kinetics, δcol. Collagenases are cleared at the rate αmmp. b, Left: simulation results for the effect of delivering MSCs 1 week after bleomycin (arrows) on collagenase; and right: on collagen levels in lung tissue, with βmmp varying from 0.4 to 4.0. c, Left: simulation results for the effect of delivering MSCs 3 weeks after bleomycin (arrows) on collagenase; and right: on collagen levels in lung tissue, showing βmmp = 0.4 and 1.2 without or with restoration of the maximum TNF-α level (±T) in the bleomycin-treated host. d, Simulation results for the sensitivity of collagen degradation to host TNF-α as a function of βmmp when MSCs are delivered 3 weeks after bleomycin, followed by evaluation of tissue collagen 1 week after cell delivery. Vertical and horizontal dotted lines indicate the maximum level of TNF-α after a single dose of bleomycin and the physiological level of lung tissue collagen, respectively.