State of the field: cellular and exosomal therapeutic approaches in vascular regeneration

Abstract

Pathologies of the vasculature and microvasculature are often complex in nature, leading to loss of physiological homeostatic regulation of patency and adequate perfusion to match tissue metabolic demands. Contributing pathological factors include endothelial dysfunction, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, loss of angiogenic potential and vascular density, and greater senescence and apoptosis. In many clinical settings, current pharmacologic strategies lack holistic mechanisms whilst addressing symptoms of pathology rather than their root cause. To address this, efforts have been heavily focused on cellular therapies that can tackle the multifaceted etiology of vascular and microvascular dysfunction. In this review, we discuss 1) the state of the field in terms of common therapeutic cell population isolation techniques, their unique characteristics and their advantages and disadvantages, 2) common molecular mechanisms of cell therapies to restore vascularization and/or vascular function, 3) arguments for and against allogenic vs. autologous applications of cell therapies, 4) emerging strategies to optimize and enhance cell therapies through priming and preconditioning, and finally, 5) emerging dosing and administrative strategies to bolster therapeutic effect. Significant clinical and animal studies of emerging cellular therapies to restore vascular function or pathologic tissue health by way of improved vascularization are highlighted throughout these sections.

Viewing stromal vascular fraction de novo vessel formation and association with host microvasculature using the rat mesentery culture model

“…We speculate that since SVF contains various stem cell populations, the dramatic differences in effects on microvascular growth might be attributed to SVF's mixture of multiple cell types. These differences motivate future studies to (1) compare the advantages between specific stem cell therapy approaches and (2) elucidate the roles of specific sub‐cell populations 35 …”

The Role and Mechanism of the Vascular Endothelial Niche in Diseases: A Review

“… a) Vascular endothelial cells can form channels in the blood vessel niche to facilitate invasion of molecules into specific tissues or organs. Under normal circumstances, vascular endothelium has its specific morphology and process unabnormal hyperplasia ( Tracy et al, 2022 ). The research has uncovered that when body undergone disruption with tumor or inflammation, vascular endothelial cells proliferated to form a new vascular channel morphology.…”

A Challenge for Engineering Biomimetic Microvascular Models: How do we Incorporate the Physiology?

“…In order to mimic the microvasculature, multiple cells must be spatially assembled in relevant patterns. As an alternative bottom-up approach to build vessels, stem cell populations have been used as heterogeneous cell sources based on the premise that stem cells can undergo appropriate differentiation or even self-assemble into capillary networks ( Kusuma et al, 2013 ; Zanotelli et al, 2016 ; Jones et al, 2021 ; Tracy et al, 2022 ). Regardless of the approach, the tissue engineering challenge of mimicking physiological relevance is highlighted by comparison to a real network ( Figure 1 ).…”