No Identical "Mesenchymal Stem Cells" at Different Times and Sites: Human Committed Progenitors of Distinct Origin and Differentiation Potential Are Incorporated as Adventitial Cells in Microvessels.
A widely shared view reads that mesenchymal stem/stromal cells ("MSCs") are ubiquitous in human connective tissues, can be defined by a common in vitro phenotype, share a skeletogenic potential as assessed by in vitro differentiation assays, and coincide with ubiquitous pericytes. Using stringent in vivo differentiation assays and transcriptome analysis, we show that human cell populations from different anatomical sources, regarded as "MSCs" based on these criteria and assumptions, actually differ widely in their transcriptomic signature and in vivo differentiation potential. In contrast, they share the capacity to guide the assembly of functional microvessels in vivo, regardless of their anatomical source, or in situ identity as perivascular or circulating cells. This analysis reveals that muscle pericytes, which are not spontaneously osteochondrogenic as previously claimed, may indeed coincide with an ectopic perivascular subset of committed myogenic cells similar to satellite cells. Cord blood-derived stromal cells, on the other hand, display the unique capacity to form cartilage in vivo spontaneously, in addition to an assayable osteogenic capacity. These data suggest the need to revise current misconceptions on the origin and function of so-called "MSCs," with important applicative implications. The data also support the view that rather than a uniform class of "MSCs," different mesoderm derivatives include distinct classes of tissue-specific committed progenitors, possibly of different developmental origin.
Stem Cell Lab, Department of Molecular Medicine, Sapienza University of Rome, Rome 00161, Italy.
Benedetto
B
Sacchetti
Stem Cell Lab, Department of Molecular Medicine, Sapienza University of Rome, Rome 00161, Italy.
Alessia
A
Funari
Stem Cell Lab, Department of Molecular Medicine, Sapienza University of Rome, Rome 00161, Italy.
Cristina
C
Remoli
Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome 00158, Italy.
Giuseppe
G
Giannicola
Institute for Transplant Diagnostics and Cellular Therapeutics, Medical Center Heinrich-Heine University, Duesseldorf 40225, Germany.
Gesine
G
Kogler
Institute for Transplant Diagnostics and Cellular Therapeutics, Medical Center Heinrich-Heine University, Duesseldorf 40225, Germany.
Stefanie
S
Liedtke
Institute of Inflammation and Repair, University of Manchester, Manchester M13 9PL, UK.
Giulio
G
Cossu
Dulbecco Telethon Institute, Pediatric Department, Tettamanti Research Center, University of Milano-Bicocca, San Gerardo Hospital, Monza 20900, Italy.
Marta
M
Serafini
Department of Development and Regeneration, KU Leuven, Leuven 3000, Belgium.
Maurilio
M
Sampaolesi
Center for Genome Research, University of Modena and Reggio Emilia, Modena 41121, Italy.
Enrico
E
Tagliafico
Center for Genome Research, University of Modena and Reggio Emilia, Modena 41121, Italy.
Elena
E
Tenedini
Department of Biology and Biotechnology "C. Darwin", Sapienza University, IBPM CNR, Rome 00185, Italy.
Isabella
I
Saggio
Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA. Electronic address: probey@dir.nidcr.nih.gov.
Pamela G
PG
Robey
Stem Cell Lab, Department of Molecular Medicine, Sapienza University of Rome, Rome 00161, Italy. Electronic address: mara.riminucci@uniroma1.it.
Mara
M
Riminucci
Stem Cell Lab, Department of Molecular Medicine, Sapienza University of Rome, Rome 00161, Italy.
Paolo
P
Bianco
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage / Q000235:genetics; D020219:Chondrogenesis / Q000235:genetics; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D055806:Microvessels / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics; D020286:Pericytes / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology* / Q000378:metabolism; D059467:Transcriptome; D014183:Transplantation, Heterologous
D015415:Biomarkers
bone marrow stromal cell; differentiation; hematopoietic microenvironment; in vivo assays; mesenchymal stem cell; myogenic progenitors; skeletal progenitors; transplantation