Neural network analysis of ex-vivo expansion of hematopoietic stem cells.

The shortage of hematopoietic stem cells (HSCs) greatly limits their widespread clinical applications. Few studies however, investigated the relationship between the cellular expansion and the influencing factors although wide variety results of the ex-vivo expansion of HSCs existed in literature. Here, a back-propagation (BP) neural network model was employed to evaluate the ex-vivo expansions of nuclear cells (NCs), CD34(+) cells, and colony-forming units (CFU-Cs), where the output was the cellular expansion folds and the inputs include inoculated density, cytokines, resources, serum, stroma, culture time, and bioreactor types. Around 124, 86, and 90 samples were used to train the neural network for the expansion evaluations of NCs, CD34(+ )cells, and CFU-Cs, respectively, while 17, 14, and 10 samples were applied to predict respectively. The results show that for the training of network, the interval accuracy of the expansion folds for the different cells is 85.5, 86.1, and 86.7%, respectively, while the truth-value accuracy is still up to 59.7, 50.0, and 62.2%, respectively within a relative error (RE) of +/-20%. For the prediction of network, the interval accuracy can be up to 82.4, 71.4, and 70%, respectively, while the truth-value accuracy is only 29.4, 14.3, and 50.0%, respectively (RE = +/-20%). Moreover, six verification experiments were carried out based on our interval predicted values and the results proved that the five group predicted conditions lead to the correct expansion of the HSCs with the accuracy more than 80%. Considering the complexity of HSC expansion and complicated wide range of the experimental data, such relatively high interval accuracy for training and prediction as well as verification are satisfied. Therefore this nonlinear modeling makes it possible to describe quantitatively the effects of the culture conditions on the HSC expansion and to predict the optimal culture conditions for higher ex-vivo expansion of HSCs.