Tissue-Specific Cultured Human Pericytes: Perivascular Cells from Smooth Muscle Tissue Have Restricted Mesodermal Differentiation Ability
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Updated: Mar 24, 2026
Isolation and Purification of Murine Cardiac Pericytes
Published on: August 16, 2019
Enrico Pierantozzi1, Bianca Vezzani1, Margherita Badin1
11 Molecular Medicine Section, University of Siena , Siena, Italy .
Abstract:
Microvascular pericytes (PCs) are considered the adult counterpart of the embryonic mesoangioblasts, which represent a multipotent cell population that resides in the dorsal aorta of the developing embryo. Although PCs have been isolated from several adult organs and tissues, it is still controversial whether PCs from different tissues exhibit distinct differentiation potentials. To address this point, we investigated the differentiation potentials of isogenic human cultured PCs isolated from skeletal (sk-hPCs) and smooth muscle tissues (sm-hPCs). We found that both sk-hPCs and sm-hPCs expressed known pericytic markers and did not express endothelial, hematopoietic, and myogenic markers. Both sk-hPCs and sm-hPCs were able to differentiate into smooth muscle cells. In contrast, sk-hPCs, but not sm-hPCs, differentiated in skeletal muscle cells and osteocytes. Given the reported ability of the Notch pathway to regulate skeletal muscle and osteogenic differentiation, sk-hPCs and sm-hPCs were treated with N-[N-(3,5- difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), a known inhibitor of Notch signaling. DAPT treatment, as assessed by histological and molecular analysis, enhanced myogenic differentiation and abolished osteogenic potential of sk-hPCs. In contrast, DAPT treatment did not affect either myogenic or osteogenic differentiation of sm-hPCs. In summary, these results indicate that, despite being isolated from the same anatomical niche, cultured PCs from skeletal muscle and smooth muscle tissues display distinct differentiation abilities.
Insights
Human pericytes (PCs) from skeletal and smooth muscle tissues show distinct differentiation potentials. Skeletal muscle pericytes differentiate into muscle and bone cells, while smooth muscle pericytes only form smooth muscle cells.
Area of Science:
- Cell Biology
- Stem Cell Research
- Tissue Engineering
Background:
- Microvascular pericytes (PCs) are multipotent cells originating from embryonic mesoangioblasts.
- The differentiation potential of PCs from different adult tissues remains controversial.
- Understanding PC differentiation is crucial for regenerative medicine and tissue repair.
Purpose of the Study:
- To investigate and compare the differentiation potentials of human pericytes from skeletal muscle (sk-hPCs) and smooth muscle (sm-hPCs).
- To explore the role of the Notch signaling pathway in regulating PC differentiation.
- To determine if tissue origin influences the multipotency of adult pericytes.
Main Methods:
- Isolation and culture of isogenic human pericytes from skeletal and smooth muscle tissues.
- Assessment of pericyte markers and differentiation into various cell types (smooth muscle, skeletal muscle, osteocytes).
- Inhibition of Notch signaling using DAPT and evaluation of its effects on differentiation.
Main Results:
- Both sk-hPCs and sm-hPCs expressed pericytic markers and could differentiate into smooth muscle cells.
- sk-hPCs, but not sm-hPCs, differentiated into skeletal muscle cells and osteocytes.
- Notch inhibition (DAPT) enhanced myogenic differentiation and abolished osteogenic potential in sk-hPCs, with no effect on sm-hPCs.
Conclusions:
- Cultured pericytes from skeletal and smooth muscle tissues exhibit distinct differentiation abilities, despite originating from similar anatomical niches.
- The Notch pathway plays a role in regulating the skeletal and osteogenic differentiation potential of skeletal muscle-derived pericytes.
- These findings highlight the importance of tissue source in determining pericyte function and potential therapeutic applications.
