Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Multi-omics characterization of mesenchymal stem/stromal cells for the identification of putative critical quality attributes BackgroundMesenchymal stromal cells (MSCs) have shown great promise in the field of regenerative medicine as many studies have shown that MSCs possess immunomodulatory function. Despite this promise, no MSC therapies have been granted licensure from the FDA. This lack of successful clinical translation is due in part to MSC heterogeneity and a lack of critical quality attributes (CQAs). While MSC Indoleamine 2,3-dioxygnease (IDO) activity has been shown to correlate with MSC function, multiple CQAs may be needed to better predict MSC function.

MethodsThree MSC lines (two bone marrow, one iPSC) were expanded to three passages. At the time of harvest for each passage, cell pellets were collected for nuclear magnetic resonance (NMR) and ultra-performance liquid chromatography mass spectrometry (UPLC-MS), and media was collected for cytokine profiling. Harvested cells were also cryopreserved for assessing function using T cell proliferation and IDO activity assays. Linear regression was performed on functional and multiomics data to reduce the number of important features, and partial least squares regression (PLSR) was used to obtain putative CQAs based on variable importance in projection (VIP) scores.

ResultsSignificant functional heterogeneity (in terms of T cell suppression and IDO activity) was observed between the three MSC lines, as well as donor-dependent differences based on passage. Omics characterization revealed distinct differences between cell lines using principal component analysis (PCA). Cell lines separated along principal component 1 based on tissue source (bone marrow vs. iPSC-derived) for NMR, MS, and cytokine profiles. PLSR modeling of important features predicts MSC functional capacity with NMR (R2=0.86), MS (R2=0.83), cytokines (R2=0.70), and a combination of all features (R2=0.88).

DiscussionThe work described here provides a platform for identifying putative CQAs for predicting MSC functional capacity using PLSR modeling that could be used as release criteria and guide future manufacturing strategies for MSCs and other cell therapies.
3
The categories of this paper are: evolutionary
23
The categories of this paper are: immunology
17
The categories of this paper are: molecular
10
The categories of this paper are: and
7
The categories of this paper are: ecology
29
The categories of this paper are: education
30
The categories of this paper are: scientific
27
The categories of this paper are: pathology
12
The categories of this paper are: behavior
19
The categories of this paper are: epidemiology
6
The categories of this paper are: plant
8
The categories of this paper are: genomics
9
The categories of this paper are: synthetic
26
The categories of this paper are: biochemistry
14
The categories of this paper are: biophysics
32
The categories of this paper are: zoology