Current Stem Cell Research & Therapy - Volume 15, Issue 5, 2020

Persistent and transient mechanical loads can act as biological signals on all levels of an organism. It is therefore not surprising that most cell types can sense and respond to mechanical loads, similar to their interaction with biochemical and electrical signals. The presence or absence of mechanical forces can be an important determinant of form, function and health of many tissue types. Along with naturally occurring mechanical loads, it is possible to manipulate and apply external physical loads on tissues in biomedical sciences, either for prevention or treatment of catabolism related to many factors, including aging, paralysis, sedentary lifestyles and spaceflight. Mechanical loads consist of many components in their applied signal form such as magnitude, frequency, duration and intervals. Even though high magnitude mechanical loads with low frequencies (e.g. running or weight lifting) induce anabolism in musculoskeletal tissues, their applicability as anabolic agents is limited because of the required compliance and physical health of the target population. On the other hand, it is possible to use low magnitude and high frequency (e.g. in a vibratory form) mechanical loads for anabolism as well. Cells, including stem cells of the musculoskeletal tissue, are sensitive to high frequency, lowintensity mechanical signals. This sensitivity can be utilized not only for the targeted treatment of tissues, but also for stem cell expansion, differentiation and biomaterial interaction in tissue engineering applications. In this review, we reported recent advances in the application of low-intensity vibrations on stem and progenitor cell populations. Modulation of cellular behavior with low-intensity vibrations as an alternative or complementary factor to biochemical and scaffold induced signals may represent an increase of capabilities in studies related to tissue engineering.

Background: Stem cells have attracted the researchers interest, due to their applications in regenerative medicine. Their self-renewal capacity for multipotent differentiation, and immunomodulatory properties make them unique to significantly contribute to tissue repair and regeneration applications. Recently, stem cells have shown increased proliferation when irradiated with low-level laser therapy or Photobiomodulation Therapy (PBMT), which induces the activation of intracellular and extracellular chromophores and the initiation of cellular signaling. The purpose of this study was to evaluate this phenomenon in the literature. Methods: The literature investigated the articles written in English in four electronic databases of PubMed, Scopus, Google Scholar and Cochrane up to April 2019. Stem cell was searched by combining the search keyword of "low-level laser therapy" OR "low power laser therapy" OR "low-intensity laser therapy" OR "photobiomodulation therapy" OR "photo biostimulation therapy" OR "LED". In total, 46 articles were eligible for evaluation. Results: Studies demonstrated that red to near-infrared light is absorbed by the mitochondrial respiratory chain. Mitochondria are significant sources of reactive oxygen species (ROS). Mitochondria play an important role in metabolism, energy generation, and are also involved in mediating the effects induced by PBMT. PBMT may result in the increased production of (ROS), nitric oxide (NO), adenosine triphosphate (ATP), and cyclic adenosine monophosphate (cAMP). These changes, in turn, initiate cell proliferation and induce the signal cascade effect. Conclusion: The findings of this review suggest that PBMT-based regenerative medicine could be a useful tool for future advances in tissue engineering and cell therapy.

Mesenchymal stem cells (MSCs) are multipotent stromal cells, with the ability to differentiate into mesodermal (e.g., adipocyte, chondrocyte, hematopoietic, myocyte, osteoblast), ectodermal (e.g., epithelial, neural) and endodermal (e.g., hepatocyte, islet cell) lineages based on the type of induction cues provided. As compared to embryonic stem cells, MSCs hold a multitude of advantages from a clinical translation perspective, including ease of isolation, low immunogenicity and limited ethical concerns. Therefore, MSCs are a promising stem cell source for different regenerative medicine applications. The in vitro differentiation of MSCs into different lineages relies on effective mimicking of the in vivo milieu, including both biochemical and mechanical stimuli. As compared to other biophysical cues, such as substrate stiffness and topography, the role of fluid shear stress (SS) in regulating MSC differentiation has been investigated to a lesser extent although the role of interstitial fluid and vascular flow in regulating the normal physiology of bone, muscle and cardiovascular tissues is well-known. This review aims to summarise the current state-of-the-art regarding the role of SS in the differentiation of MSCs into osteogenic, cardiovascular, chondrogenic, adipogenic and neurogenic lineages. We will also highlight and discuss the potential of employing SS to augment the differentiation of MSCs to other lineages, where SS is known to play a role physiologically but has not yet been successfully harnessed for in vitro differentiation, including liver, kidney and corneal tissue lineage cells. The incorporation of SS, in combination with biochemical and biophysical cues during MSC differentiation, may provide a promising avenue to improve the functionality of the differentiated cells by more closely mimicking the in vivo milieu.

At present, many kinds of materials are used for bone tissue engineering, such as polymer materials, metals, etc., which in general have good biocompatibility and mechanical properties. However, these materials cannot be controlled artificially after implantation, which may result in poor repair performance. The appearance of the magnetic response material enables the scaffolds to have the corresponding ability to the external magnetic field. Within the magnetic field, the magnetic response material can achieve the targeted release of the drug, improve the performance of the scaffold, and further have a positive impact on bone formation. This paper first reviewed the preparation methods of magnetic responsive materials such as magnetic nanoparticles, magnetic polymers, magnetic bioceramic materials and magnetic alloys in recent years, and then introduced its main applications in the field of bone tissue engineering, including promoting osteogenic differentiation, targets release, bioimaging, cell patterning, etc. Finally, the mechanism of magnetic response materials to promote bone regeneration was introduced. The combination of magnetic field treatment methods will bring significant progress to regenerative medicine and help to improve the treatment of bone defects and promote bone tissue repair.

Recent interest in developing new regenerative medicine- and tissue engineering-based treatments has motivated researchers to develop strategies for manipulating stem cells to optimize outcomes in these potentially, game-changing treatments. Cells communicate with each other, and with their surrounding tissues and organs via electrochemical signals. These signals originate from ions passing back and forth through cell membranes and play a key role in regulating cell function during embryonic development, healing, and regeneration. To study the effects of electrical signals on cell function, investigators have exposed cells to exogenous electrical stimulation and have been able to increase, decrease and entirely block cell proliferation, differentiation, migration, alignment, and adherence to scaffold materials. In this review, we discuss research focused on the use of electrical stimulation to manipulate stem cell function with a focus on its incorporation in tissue engineering-based treatments.

Differentiation of stem cells, a crucial step in the process of tissue development, repair and regeneration, can be regulated by a variety of mechanical factors such as the stiffness of extracellular matrix. In this review article, the effects of stiffness on the differentiation of stem cells, including bone marrow-derived stem cells, adipose-derived stem cells and neural stem cells, are briefly summarized. Compared to two-dimensional (2D) surfaces, three-dimensional (3D) hydrogel systems better resemble the native environment in the body. Hence, the studies which explore the effects of stiffness on stem cell differentiation in 3D environments are specifically introduced. Integrin is a well-known transmembrane molecule, which plays an important role in the mechanotransduction process. In this review, several integrin-associated signaling molecules, including caveolin, piezo and Yes-associated protein (YAP), are also introduced. In addition, as stiffness-mediated cell differentiation may be affected by other factors, the combined effects of matrix stiffness and viscoelasticity, surface topography, chemical composition, and external mechanical stimuli on cell differentiation are also summarized.

Objective: This is a systematic review of the effects of low-intensity pulsed ultrasound (LIPUS) on stem cell differentiation. Background Data: Recent studies have investigated several types of stem cells from different sources in the body. These stem cells should strictly be certified and promoted for cell therapies before being used in medical applications. LIPUS has been used extensively in treatment centers and in research to promote stem cell differentiation, function, and proliferation. Materials and Methods: The databases of PubMed, Google Scholar, and Scopus were searched for abstracts and full-text scientific papers published from 1989-2019 that reported the application of LIPUS on stem cell differentiation. Related English language articles were found using the following defined keywords: low-intensity pulsed ultrasound, stem cell, differentiation. Criteria for inclusion in the review were: LIPUS with frequencies of 1–3 MHz and pulsed ultrasound intensity of <500 mW/cm2. Duration, exposure time, and cell sources were taken into consideration. Results: Fifty-two articles were selected based on the inclusion criteria. Most articles demonstrated that the application of LIPUS had positive effects on stem cell differentiation. However, some authors recommended that LIPUS combined with other physical therapy aides was more effective in stem cell differentiation. Conclusion: LIPUS significantly increases the level of stem cell differentiation in cells derived mainly from bone marrow mesenchymal stem cells. There is a need for further studies to analyze the effect of LIPUS on cells derived from other sources, particularly adipose tissue-derived mesenchymal stem cells, for treating hard diseases, such as osteoporosis and diabetic foot ulcer. Due to a lack of reporting on standard LIPUS parameters in the field, more experiments comparing the protocols for standardization of LIPUS parameters are needed to establish the best protocol, which would allow for the best results.