Adult stem cells that are tightly regulated by the specific microenvironment, or the stem cell niche, function to maintain tissue homeostasis and regeneration after damage. This demands the existence of specific niche components that can preserve the stem cell pool in injured tissues and restore the microenvironment for their subsequent appropriate functioning. This role may belong to mesenchymal stromal cells (MSCs) due to their resistance to damage signals and potency to be specifically activated in response to tissue injury and promote regeneration by different mechanisms. Increased amount of data indicate that activated MSCs are able to produce factors such as extracellular matrix components, growth factors, extracellular vesicles and organelles, which transiently substitute the regulatory signals from missing niche cells and restrict the injury-induced responses of them. MSCs may recruit functional cells into a niche or differentiate into missing cell components to endow a niche with ability to regulate stem cell fates. They may also promote the dedifferentiation of committed cells to re-establish a pool of functional stem cells after injury. Accumulated evidence indicates the therapeutic promise of MSCs for stimulating tissue regeneration, but the benefits of administered MSCs demonstrated in many injury models are less than expected in clinical studies. This emphasizes the importance of considering the mechanisms of endogenous MSC functioning for the development of effective approaches to their pharmacological activation or mimicking their effects. To achieve this goal, we integrate the current ideas on the contribution of MSCs in restoring the stem cell niches after damage and thereby tissue regeneration.

受特定微环境或干细胞生态位严格调控的成年干细胞的功能是在损伤后维持组织稳态和再生。这就要求存在特定的利基成分，这些成分可以在受损组织中保存干细胞库并恢复微环境，以使其随后的适当功能发挥作用。这种作用可能属于间充质基质细胞（MSC），因为它们对损伤信号具有抵抗力，并具有响应组织损伤而被特异性激活并通过不同机制促进再生的能力。越来越多的数据表明，活化的MSC能够产生诸如细胞外基质成分，生长因子，细胞外囊泡和细胞器等因子，它瞬时替代了缺失的利基细胞的调节信号，并限制了损伤诱导的反应。MSC可将功能细胞募集到适当位置或分化成缺失的细胞成分，从而赋予适当位置调节干细胞命运的能力。它们还可以促进定型细胞的去分化，从而在损伤后重新建立功能性干细胞库。积累的证据表明，MSC具有刺激组织再生的治疗前景，但是在许多损伤模型中证明的MSC给药的益处低于临床研究的预期。这强调了考虑内源性MSC的功能机制以开发有效的药理激活或模拟其作用的方法的重要性。为了实现这个目标，