Smooth muscle cells

The force of internal dynamics

Credit: Art by Nelly Aghekyan. Set in motion by Dr. Emanuele Petretto. Words by Dr. Agnieszka Szmitkowska. Project coordination: Dr. Masia Maksymowicz. Series Director: @Radhika Patnala Sci-illustrate Endosymbiont

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Irreplaceable workers of internal systems

Smooth muscle cells (SMCs) are irreplaceable yet often underappreciated components of the musculoskeletal system and the third type of muscle cells in our series. Beyond their basic identification as non-striated muscle cells, they are involved in functioning of numerous organ systems, including the vascular, gastrointestinal, and urogenital. Smooth muscle cells are a specialised type of muscle cells predominantly found in the walls of hollow organs such as the intestines, bladder, and blood vessels, which coordinate their delicate but crucial contractions and tone (1).

The structure of smooth muscle cells

Smooth muscle cells are not striped like skeletal or cardiac muscle cells. Their lack of visible stripes or striations is due to the cell’s different arrangement of actin and myosin filaments. Those cells are typically spindle-shaped with a single, centrally located nucleus. Their length can vary greatly, ranging from a few micrometres in the smallest blood vessels to several millimetres in large arteries (2).

The unique structural organization of SMCs is closely linked to their functional role. The actin and myosin filaments are arranged diagonally in the cytoplasm, allowing for a more sustained and less forceful contraction than the rapid and powerful contractions seen in striated muscles. This is particularly important for organs that require continuous, low-level force, such as blood vessels maintaining vascular tone and the gastrointestinal tract moving contents via peristalsis (3).

Contractions of SMCs

Smooth muscle cells have a unique activation mode compared to skeletal and cardiac muscles. While skeletal muscle contracts mainly in response to voluntary neural signals, SMCs can be activated through various methods, including inputs from the autonomic nervous system, hormonal influences, and changes in local chemical conditions. For example, substances like nitric oxide released by the endothelium in blood vessels can cause the smooth muscle layer to relax, resulting in vasodilation — the widening of blood vessels (4).

A notable characteristic of smooth muscle cells is their capacity to sustain tension for long periods without becoming fatigued. This endurance is caused by latch-state mechanics, wherein the myosin heads stay attached to actin filaments for an extended time. This process minimises the need for ATP hydrolysis and conserves energy. Such mechanism is crucial in regulating blood pressure within the systemic circulation (5).

Diseases of smooth muscle cells

Alterations in SMC function are implicated in conditions like asthma, where bronchial SMC contraction leads to airway narrowing, and irritable bowel syndrome, where dysregulation of intestinal SMCs affects gut motility (6).

An important aspect of SMCs is their role in the development of hypertension. In hypertensive states, blood vessel remodelling often involves hyperplasia and/or hypertrophy of SMCs, leading to increased vascular resistance. The underlying molecular mechanisms often involve alterations in calcium handling, changes in receptor sensitivity, and activation of various signalling pathways, such as those mediated by angiotensin II or endothelin-1 (7).

Power of regeneration

Smooth muscle cells have a remarkable regeneration capacity that distinguishes them from other types of muscle cells. This regeneration ability is very important since it allows smooth muscle tissues to heal and replenish themselves throughout an individual’s life.

Smooth muscle cells are continually exposed to numerous stresses and stimuli in many body regions, including the walls of blood vessels, the bladder, and the digestive tract. The ability of smooth muscle cells to regenerate guarantees that these tissues can recover from harm and adapt to changes in their surroundings. Smooth muscle cells, for example, can proliferate and mend the artery wall following an injury or adapt to variations in blood pressure or flow (8).

Regeneration is accomplished by allowing smooth muscle cells to re-enter the cell cycle to proliferate and replace injured or aged cells. In contrast, skeletal muscle cells have a minimal ability to regenerate, while cardiac muscle cells are largely incapable of replicating after birth. Smooth muscle cell regeneration ability is critical for preserving the body’s functionality and integrity of the abovementioned organ systems (9).

Regenerative medicine

SMCs are a focus in regenerative medicine and tissue engineering. One of the most significant advancements in utilizing SMCs in regenerative medicine has been in vascular tissue engineering. The development of artificial blood vessels, crucial for coronary bypass surgery and other vascular grafts, relies heavily on the functional integration of SMCs. These cells contribute to engineered vessels’ structural integrity and functionality by producing extracellular matrix components and regulating vascular tone. Their ability to synthesize collagen, elastin, and other matrix proteins ensures the mechanical stability and elasticity of the engineered tissues, mimicking natural blood vessels (10, 11).

Another area where SMCs have shown promising is in the regeneration of the urinary bladder. Researchers have successfully used SMCs in combination with biodegradable scaffolds to engineer bladder tissues. These engineered tissues have been shown to integrate well with the host’s native tissue, restoring normal bladder function. This approach demonstrates the potential of SMCs in organ regeneration, opening doors for future applications in other organ systems (12).

Conclusions

The unique structure and ability to sustain prolonged contractions without fatigue make smooth muscle cells indispensable in regulating blood pressure, gastrointestinal motility, and urinary control. The involvement of SMCs in diseases such as asthma, irritable bowel syndrome, and hypertension highlights their clinical significance. Moreover, their remarkable regenerative capacity allows for the maintenance and repair of vital tissues and positions them at the forefront of regenerative medicine and tissue engineering. The advances in using SMCs to develop artificial blood vessels and regenerate bladder tissue underscore their potential in medical science. As research continues, understanding the SMCs’ properties could lead to significant breakthroughs in treating various disorders and improving overall health.

Recognising labs working on the subject:

1. Lilly lab. Center for Cardiovascular Research Abigail Wexner Research Institute Nationwide Children’s Hospital Research, Columbus, Ohio, USA https://www.nationwidechildrens.org/research/areas-of-research/center-for-cardiovascular-research/lilly-lab @nationwidekids
2. The Zheng Lab , Vascular Smooth Muscle and Human Diseases, Cumming School Of Medicine, University Of Calgary , Canada, @Ucalgarymed, https://cumming.ucalgary.ca/labs/vascular-smooth-muscle/vascular-smooth-muscle
3. The Lucy Liaw Lab, Endothelial and Smooth Muscle Cell Development, Graduate School of Biomedical Sciences, Tufts University, Medford, MA, USA, https://gsbs.tufts.edu/faculty-research/lucy-liaw-lab
4. Microcirculation Laboratory, School of Medicine, University of Missouri, USA, https://medicine.missouri.edu/centers-institutes-labs/microcirculation-laboratory
5. Research Institute of Experimental Biology and Medicine, Burdenko Voronezh State Medical University, Voronezh, Russia, https://vrngmu.ru/english/about-vsma/
6. Institute for Hematopathology, 22547 Hamburg, Germany, https://www.haematopathologie-hamburg.de/
7. Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, Cambridge, UK, https://www.med.cam.ac.uk/cardiovascular-medicine-2/
8. INSERM U970, Paris Cardiovascular Research Center, Paris, France, https://parcc.inserm.fr/
9. Center for Developmental Biology and Regenerative Medicine, Seattle Children’s Research Institute, and Departments of Pediatrics and Pathology, University of Washington, USA, https://www.seattlechildrens.org/research/centers-programs/developmental-biology-regenerative-medicine/

References

1. Hafen BB, Shook M, Burns B. Anatomy, Soft Skelett.
2. Garfield R, Somlyo A. Structure of smooth muscle. Calcium and Contractility: Smooth Muscle: Springer; 1985. p. 1–36.
3. Williams B. Mechanical influences on vascular smooth muscle cell function. Journal of hypertension. 1998;16(12):1921–9.
4. Webb RC. Smooth muscle contraction and relaxation. Advances in physiology education. 2003;27(4):201–6.
5. Roby T, Olsen S, Nagatomi J. Effect of sustained tension on bladder smooth muscle cells in three-dimensional culture. Annals of biomedical engineering. 2008;36:1744–51.
6. Michel J-B, Li Z, Lacolley P. Smooth muscle cells and vascular diseases. Oxford University Press; 2012. p. 135–7.
7. Touyz RM, Alves-Lopes R, Rios FJ, Camargo LL, Anagnostopoulou A, Arner A, et al. Vascular smooth muscle contraction in hypertension. Cardiovascular research. 2018;114(4):529–39.
8. Curcio A, Torella D, Indolfi C. Mechanisms of Smooth Muscle Cell Proliferation and Endothelial Regeneration After Vascular Injury and Stenting–Approach to Therapy–. Circulation Journal. 2011;75(6):1287–96.
9. Kanematsu A, Yamamoto S, Iwai-Kanai E, Kanatani I, Imamura M, Adam RM, et al. Induction of smooth muscle cell-like phenotype in marrow-derived cells among regenerating urinary bladder smooth muscle cells. The American journal of pathology. 2005;166(2):565–73.
10. De Villiers JA, Houreld N, Abrahamse H. Adipose derived stem cells and smooth muscle cells: implications for regenerative medicine. Stem Cell Reviews and Reports. 2009;5:256–65.
11. Crisan M, Corselli M, Chen WC, Péault B. Perivascular cells for regenerative medicine. Journal of cellular and molecular medicine. 2012;16(12):2851–60.
12. Zhou L, Xia J, Wang P, Jia R, Zheng J, Yao X, et al. Autologous smooth muscle progenitor cells enhance regeneration of tissue-engineered bladder. Tissue Engineering Part A. 2018;24(13–14):1066–81.

About the author:

DR. AGA SZMITKOWSKA

Content Editor The League of Extraordinary Celltypes, Sci-Illustrate Stories

Aga did her Ph.D. in Biochemistry at the CEITEC/Masaryk University in Brno, Czech Republic, where she was a part of the Laboratory of Genomics and Proteomics of Plant Systems. She is a passionate public speaker and science communicator. After graduation, she became a freelance content coordinator and strategist in a start-up environment focused on lifestyle and longevity.

About the artist:

NELLY AGHEKYAN

Contributing Artist The League of Extraordinary Cell Types, Sci-Illustrate Stories

Nelli Aghekyan, did a bachelor’s and master’s in Architecture in Armenia, after studying architecture and interior design for 6 years, she concentrated on her drawing skills and continued her path in the illustration world. She works mainly on children’s book illustrations, some of her books are now being published. Currently living in Italy, she works as a full-time freelance artist, collaborating with different companies and clients.

About the animator:

DR. EMANUELE PETRETTO

Animator The League of Extraordinary Celltypes, Sci-Illustrate Stories

Dr. Petretto received his Ph.D. in Biochemistry at the University of Fribourg, Switzerland, focusing on the behaviour of matter at nanoscopic scales and the stability of colloidal systems. Using molecular dynamics simulations, he explored the delicate interaction among particles, interfaces, and solvents.

Currently, he is fully pursuing another delicate interaction: the intricate interplay between art and science. Through data visualisation, motion design, and games, he wants to show the wonders of the complexity surrounding us.

About the series: The League of Extraordinary Celltypes

The team at Sci-Illustrate and Endosymbiont bring to you an exciting series where we dive deep into the wondrous cell types that make our bodies tick ❤.

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