Functional prediction of cellular functions by means of microrna expresssion profiling in mesenchymal stem cells

Abstract

Non-coding RNA, such as miRNA, expression data derived from a cell population is used to infer the propensity of that cell population for a cellular functional effect for a pre-determined purpose, which effect is temporally, procedurally or interventionally separated from the cell population from which the expression data is derived. Thereby, the cellular functional effect of a cell population can be predicted in order to improve decisions and selections to be made relating to the use of cells, e.g. from cells deriving from different donors or batches, for use in bioprocess application or cell therapeutics, in order to enhance productivity, efficiency and/or efficacy.

1 . A method of inferring propensity of a cell population for a cellular functional effect for a pre-determined purpose, the method comprising assaying the cell population against a pre-determined non-coding RNA or panel of non-coding RNAs known or determined to correlate with the cellular functional effect, generating non-coding RNA expression data for the assayed non-coding RNA or panel of non-coding RNAs and from the non-coding RNA expression data identifying, determining or inferring a propensity for the cellular functional effect, wherein the cellular functional effect is a functional effect of a cell population which effect is temporally, procedurally or interventionally separated from the cell population from which the expression data or expression profiles derive. 
     
     
         2 . The method as claimed in  claim 1 , wherein the identifying, determining or inferring a propensity for the cellular functional effect is by comparing the expression data from the assay with expression levels, trends or patterns known to be associated with cellular functional effect. 
     
     
         3 . The method as claimed in  claim 1 , which is for inferring a cellular functional effect in a cell population by assaying that cell population against the predetermined non-coding RNA or panel of non-coding RNAs. 
     
     
         4 . The method as claimed in  claim 1 , wherein the panel of non-coding RNA comprises at least two non-coding RNA and preferably up to six non-coding RNA. 
     
     
         5 . The method as claimed in  claim 4 , wherein at least one non-coding RNA is positively correlated and at least one non-coding RNA is negatively correlated with the cellular functional effect. 
     
     
         6 . The method as claimed in  claim 1 , wherein the pre-determined purpose is selected from a bioprocess applications, a cell therapy application, patient stratification for cell therapy, cell growth and donor selection. 
     
     
         7 . The method as claimed in  claim 1 , wherein the cellular functional effect is an effect on an applied cell population by a tissue to which it is applied, an effect on a tissue to which a cell population is applied, production of paracrine factors, proliferation activity, differentiation tendency, engraftment potential, immunosuppressive activity, migration potential, response to activity inducing agents or response to assays. 
     
     
         8 . The method as claimed in  claim 1 , which further comprises making a selection or treatment decision based upon the identification, determination or inference of propensity for the cellular functional effect. 
     
     
         9 . A method of treatment of a human or animal patient in need thereof, the method comprising administering one or a plurality of cell therapy doses to said patient, said cell therapy dose effective in treating said patient by a cellular function effect as between the cell therapy and the patient, the cellular function effect having been inferred by use of non-coding RNA expression profile, by measuring the non-coding RNA expression profile for the cell therapy for a pre-determined non-coding RNA or panel of non-coding RNAs known to correlate with the cellular functional effect and inferring therefrom a relative propensity to the cellular functional effect and determining therefrom with reference to a predetermined dose for a pre-determined propensity of the one or a plurality of cell therapy doses administered to said patient. 
     
     
         10 . The method as claimed in  claim 9 , wherein the treatment is one of autologous cell therapy or allogenic cell therapy. 
     
     
         11 . A cell population for use in the treatment of a condition in a patient in need thereof, which treatment is mediated by a pre-defined cellular functional effect, the cell population provided in a dose or dosage regimen determined according to the non-coding RNA expression of the cell population for a pre-defined non-coding RNA or panel of non-coding RNAs that correlates with the cellular functional effect to a degree that corresponds with one of a plurality of possible doses or dosage regimen, by the method of  claim 9 . 
     
     
         12 . The cell population as claimed in  claim 11  which are human cells. 
     
     
         13 . The cell population as claimed in  claim 11  which cells are stem cells or T-cells. 
     
     
         14 . The cell population as claimed in  claim 13 , wherein the cells are stem cells. 
     
     
         15 . The cell population as claimed in  claim 13 , which cells are stem cells selected from MSCs, induced pluripotent stem cells or haematopoietic stem cells such as CD34+ cells. 
     
     
         16 . The cell population as claimed in  claim 15 , wherein the stem cells are MSCs. 
     
     
         17 . The cell population as claimed  claim 14 , wherein the cellular functional effect is differentiation into chondrocytes and the pre-determined purpose is regenerative treatment of cartilage tissue. 
     
     
         18 . The cell population as claimed in  claim 14 , wherein the cellular functional effect is differentiation into osteocytes and the pre-determined purpose is regenerative treatment of bone tissue. 
     
     
         19 . The cell population as claimed in  claim 14 , wherein the cellular functional effect is secretion of paracrine factors and the pre-determined purpose is regenerative treatment of target tissue. 
     
     
         20 . The cell population as claimed in  claim 14  wherein the cellular functional effect is migration toward stromal cell-derived-factor 1 (SDF-1) and the pre-determined purpose is selection of donors of stem cells for engraftment potential.