Approaches to mimic the complexity of the skeletal mesenchymal stem/stromal cell niche in vitro

Abstract

Mesenchymal stem/stromal cells (MSCs) are an essential element of most modern tissue engineering and regenerative medicine approaches due to their multipotency and immunoregulatory functions. Despite the prospective value of MSCs for the clinics, the stem cells community is questioning their developmental origin, in vivo localization, identification, and regenerative potential after several years of far-reaching research in the field. Although several major progresses have been made in mimicking the complexity of the MSC niche in vitro, there is need for comprehensive studies of fundamental mechanisms triggered by microenvironmental cues before moving to regenerative medicine cell therapy applications. The present comprehensive review extensively discusses the microenvironmental cues that influence MSC phenotype and function in health and disease-including cellular, chemical and physical interactions. The most recent and relevant illustrative examples of novel bioengineering approaches to mimic biological, chemical, and mechanical microenvironmental signals present in the native MSC niche are summarized, with special emphasis on the forefront techniques to achieve biochemical complexity and dynamic cultures. In particular, the skeletal MSC niche and applications focusing on the bone regenerative potential of MSC are addressed. The aim of the review was to recognize the limitations of the current MSC niche in vitro models and to identify potential opportunities to fill the bridge between fundamental science and clinical application of MSCs.

Safety and efficacy of allogeneic bone marrow mesenchymal stem cells for treatment of canine leukopenia induced by canine parvovirus infection

“…BMMSCs can induce the secretion of cytokines through paracrine action, such as interleukin-6, IL-12, IL-14, IL-7, IL-11, IL-15, IL-8, and some stem cell factors and colony-stimulating factors. These cytokines can promote the proliferation and differentiation of hematopoietic stem cells, thus increasing the number of cells in the blood (Pereira et al 2019). BMMSCs have immune regulatory functions, which can increase the number of blood cells by regulating the activity and differentiation of immune cells.…”

Preservation of the naïve features of mesenchymal stromal cells in vitro: Comparison of cell- and bone-derived decellularized extracellular matrix

“…Consequently, those limitations ultimately strongly influence cell biological functions and response to stimuli, 28 resulting in potentially misleading results toward clinic applications. A wide variety of material alternatives have been developed to recreate the tissuespecific ECM composition and intricate structure of stem cell niches, [29][30][31][32] albeit a single in vitro model that reproduces the in vivo microenvironment homeostasis remains a bioengineering challenge. Aiming to address this issue, decellularization of cell-derived ECM, tissues, and organs came as an ideal reverse-engineering concept able to faithfully mimic the native tissue complexity.…”

Modeling of the Human Bone Environment: Mechanical Stimuli Guide Mesenchymal Stem Cell–Extracellular Matrix Interactions

“…ECM is, in principle, a very dynamic structure that controls and is controlled by its surrounding environment, adapting its structural arrangement and composition to external stimuli [ 6 , 7 , 8 , 9 ]. In fact, bone tissue is mainly subjected to two types of mechanical signals: (1) strain caused by tension or compression triggered by physical activity, and (2) shear stress as a result of interstitial fluid movement through bone lacunae.…”

“…Yet, several limitations are raised when studying human diseases, as experimental animals often fail to recapitulate critical aspects, e.g., the age of patients and the specific human microenvironmental architecture and physiology [ 21 , 22 , 23 ]. On those grounds, over the last decade, bone tissue engineering strategies have been the focus of the research field as they allow us to recapitulate developmental processes in tridimensional (3D) in vitro settings [ 9 , 24 ]. Different types of materials have been used to engineer bone.…”