Microfluidic single-cell transcriptional analysis rationally identifies novel surface marker profiles to enhance cell-based therapies.
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.
Department of Surgery, Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
Robert C
RC
Rennert
Department of Surgery, Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.|Program in Biomedical Informatics, Stanford University School of Medicine, Stanford, California 94305, USA.
Michael
M
Januszyk
Department of Surgery, Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
Michael
M
Sorkin
Department of Surgery, Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
Melanie
M
Rodrigues
Department of Surgery, Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
Zeshaan N
ZN
Maan
Department of Surgery, Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.|Section of Plastic, Aesthetic and Reconstructive Surgery, Johannes Kepler University, Linz, Austria.|Department of Plastic Surgery and Hand Surgery, Technical University Munich, Munich, Germany.
Dominik
D
Duscher
Department of Surgery, Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
Alexander J
AJ
Whittam
Department of Surgery, Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
Revanth
R
Kosaraju
Department of Surgery, Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
Michael T
MT
Chung
Department of Surgery, Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
Kevin
K
Paik
Department of Surgery, Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
Alexander Y
AY
Li
Department of Surgery, Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.|The University of Melbourne Department of Surgery, Royal Melbourne Hospital, 300 Grattan St Parkville VIC 3068, Australia.
Michael
M
Findlay
Department of Surgery, Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
Jason P
JP
Glotzbach
Department of Pediatrics, Division of Systems Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
Atul J
AJ
Butte
Department of Surgery, Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
Geoffrey C
GC
Gurtner
D061645:Abdominoplasty; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation; D002469:Cell Separation; D002470:Cell Survival; D003920:Diabetes Mellitus / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D044085:Microfluidics; D059010:Single-Cell Analysis / Q000379:methods*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D000072836:Surgical Wound / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D014945:Wound Healing / Q000502:physiology
D015703:Antigens, CD; D015415:Biomarkers; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4