Unilineage model of hematopoiesis predicts self-renewal of stem and progenitor cells based on ex vivo growth data
✍ Scribed by Ching-An Peng; Manfred R. Koller; Bernhard Ø. Palsson
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 916 KB
- Volume
- 52
- Category
- Article
- ISSN
- 0006-3592
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✦ Synopsis
Stem cell models are used t o describe the function of several tissues. We present unilineage kinetic description of stem cell models and their application to the analysis of ex vivo hematopoietic cell expansion data. This model has the capability t o simulate the total cell number and the number of cells at each stage of differentiation over time as a function ofthe stem cell self-renewal probability, the growth rate of each subpopulation, and the mature cell death rate. The model predicts experimental observations in perfusion-based hematopoietic bioreactor sys- tems. To obtain net cell expansion ex vivo, the model simulations showthat the stem cell self-renewal probability must exceed one-half, thus resulting in net expansion of the stem cell population. Experimental data on longterm culture-initiating cells (LTC-IC) confirm this prediction and the probability of self-renewal is estimated to be 0.62 t o 0.73. This self-renewal probability, along with the death rate, define a relationship in which the apparent overall growth rate is less than the compartmental growth rate. Finally, the model predicts that cells beyond the stem cell stage of differentiation must self-renew to achieve the level of expansion within the time frame observed in experimental systems.