On self-similar growth

Ramkrishna, Doraiswami; Schell, John W.

doi:10.1016/s0168-1656(99)00030-9

Cited by 7 publications

(5 citation statements)

References 2 publications

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“…Moreover, the exclusion of cell proliferation simplified the inverse problem. Ramkrishna and co-workers have discussed the self-similar behavior of microbial systems with growth (Ramkrishna, 1994; Ramkrishna and Schell, 1999). Given that stem cell populations are not synchronized, the prospect of combined effects due to proliferation and clustering is interesting and warrants further investigation.…”

Section: Discussionmentioning

confidence: 99%

Inverse problem analysis of pluripotent stem cell aggregation dynamics in stirred-suspension cultures

Rostami

Tzanakakis

2015

Journal of Biotechnology

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The cultivation of stem cells as aggregates in scalable bioreactor cultures is an appealing modality for the large-scale manufacturing of stem cell products. Aggregation phenomena are central to such bioprocesses affecting the viability, proliferation and differentiation trajectory of stem cells but a quantitative framework is currently lacking. A population balance equation (PBE) model was used to describe the temporal evolution of the embryonic stem cell (ESC) cluster size distribution by considering collision-induced aggregation and cell proliferation in a stirred-suspension vessel. For ESC cultures at different agitation rates, the aggregation kernel representing the aggregation dynamics was successfully recovered as a solution of the inverse problem. The rate of change of the average aggregate size was greater at the intermediate rate tested suggesting a trade-off between increased collisions and agitation-induced shear. Results from forward simulation with obtained aggregation kernels were in agreement with transient aggregate size data from experiments. We conclude that the framework presented here can complement mechanistic studies offering insights into relevant stem cell clustering processes. More importantly from a process development standpoint, this strategy can be employed in the design and control of bioreactors for the generation of stem cell derivatives for drug screening, tissue engineering and regenerative medicine.

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Section: Discussionmentioning

confidence: 99%

Inverse problem analysis of pluripotent stem cell aggregation dynamics in stirred-suspension cultures

Rostami

Tzanakakis

2015

Journal of Biotechnology

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“…Building a PBM requires information at single‐cell level for calculation of intrinsic physiological state (IPS) functions; growth and division rates and partitioning probability function . Different methods have been developed to use data obtained under unbalanced or balanced growth conditions and calculate IPS functions via solving an inverse problem. But none of them has advanced to a robust methodology with general applicability.…”

Section: Bioreactor Integrated Modelsmentioning

confidence: 99%

Review of the important challenges and opportunities related to modeling of mammalian cell bioreactors

2016

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Industrialization of mammalian cell culture has been achieved by integrating knowledge from several applying core concepts of chemical engineering, cellular and molecular biology, and biochemistry. Modeling has been applied to biological and physical processes to gain additional insights into such processes. This article covers modeling of the bioreactor and metabolic processes as it applies to bioprocess. Hydrodynamics of a bioreactor is briefly described while additional focus is given to gas‐liquid mass transfer. Biological modeling is presented in the order of increasing complexity. First steady state models are presented followed by dynamic models, cybernetic models, and finally bioreactor integrated models. The closing discussion summarizes challenges of implementation of model‐based approaches in the biopharmaceutical industry. © 2016 American Institute of Chemical Engineers AIChE J, 63: 398–408, 2017

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“…Ramkrishna proposed an elegant mathematical framework to determine the IPS functions for the cell population balance problem at self-similar conditions (Ramkrishna, 1994; Ramkrishna and Schell, 1999). His idea about self-similarity is based on scaling transient flow cytometric data with appropriate cell parameters, in order to obtain time-invariant distributions of cell characteristics.…”

Section: Solving the Inverse Problemmentioning

confidence: 99%

“…A major reason for this is that the solution of CPBs requires as inputs the three IPS functions, whose determination presents significant experimental and computational challenges involving the solution of tough inverse problems (Ramkrishna, 1994; Ramkrishna et al, 1968; Ramkrishna and Schell, 1999). …”

Section: Introductionmentioning

confidence: 99%

Single-cell behavior and population heterogeneity: Solving an inverse problem to compute the intrinsic physiological state functions

Spetsieris

Zygourakis

2012

Journal of Biotechnology

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The dynamics of isogenic cell populations can be described by cell population balance models that account for phenotypic heterogeneity. To utilize the predictive power of these models, however, we must know the rates of single-cell reaction and division and the bivariate partition probability density function. These three intrinsic physiological state (IPS) functions can be obtained by solving an inverse problem that requires knowledge of the phenotypic distributions for the overall cell population, the dividing cell subpopulation and the newborn cell subpopulation. We present here a robust computational procedure that can accurately estimate the IPS functions for heterogeneous cell populations. A detailed parametric analysis shows how the accuracy of the inverse solution is affected by discretization parameters, the type of non-parametric estimators used, the qualitative characteristics of phenotypic distributions and the unknown partitioning probability density function. The effect of finite sampling and measurement errors on the accuracy of the recovered IPS functions is also assessed. Finally, we apply the procedure to estimate the IPS functions of an E. coli population carrying an IPTG-inducible genetic toggle network. This study completes the development of an integrated experimental and computational framework that can become a powerful tool for quantifying single-cell behavior using measurements from heterogeneous cell populations.

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On self-similar growth

Cited by 7 publications

References 2 publications

Inverse problem analysis of pluripotent stem cell aggregation dynamics in stirred-suspension cultures

Inverse problem analysis of pluripotent stem cell aggregation dynamics in stirred-suspension cultures

Review of the important challenges and opportunities related to modeling of mammalian cell bioreactors

Single-cell behavior and population heterogeneity: Solving an inverse problem to compute the intrinsic physiological state functions

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