Microfluidic single-cell transcriptional analysis rationally identifies novel surface marker profiles to enhance cell-based therapies

Nat Commun. 2016 Jun 21;7:11945. doi: 10.1038/ncomms11945.

Abstract

Current progenitor cell therapies have only modest efficacy, which has limited their clinical adoption. This may be the result of a cellular heterogeneity that decreases the number of functional progenitors delivered to diseased tissue, and prevents correction of underlying pathologic cell population disruptions. Here, we develop a high-resolution method of identifying phenotypically distinct progenitor cell subpopulations via single-cell transcriptional analysis and advanced bioinformatics. When combined with high-throughput cell surface marker screening, this approach facilitates the rational selection of surface markers for prospective isolation of cell subpopulations with desired transcriptional profiles. We establish the usefulness of this platform in costly and highly morbid diabetic wounds by identifying a subpopulation of progenitor cells that is dysfunctional in the diabetic state, and normalizes diabetic wound healing rates following allogeneic application. We believe this work presents a logical framework for the development of targeted cell therapies that can be customized to any clinical application.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Abdominoplasty
  • Adipocytes / cytology
  • Adipocytes / metabolism*
  • Adipose Tissue / cytology
  • Adipose Tissue / metabolism
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Biomarkers / metabolism
  • Cell Differentiation
  • Cell Lineage / genetics
  • Cell Proliferation
  • Cell Separation
  • Cell Survival
  • Diabetes Mellitus / metabolism
  • Diabetes Mellitus / pathology
  • Diabetes Mellitus / therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / therapy
  • Dipeptidyl Peptidase 4 / genetics
  • Dipeptidyl Peptidase 4 / metabolism
  • Female
  • Gene Expression
  • Humans
  • Male
  • Mice
  • Microfluidics
  • Single-Cell Analysis / methods*
  • Stem Cell Transplantation*
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Surgical Wound / metabolism
  • Surgical Wound / pathology
  • Surgical Wound / therapy*
  • Wound Healing / physiology

Substances

  • Antigens, CD
  • Biomarkers
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4