Mini review
Mini review
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DOI：
10.5924/abgri.43.1
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发表时间：
2004
影响因子：
5.2
通讯作者：
C. Raggi;A. Berardi
中科院分区：
文献类型：
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作者：
C. Raggi;A. Berardi
衰老生物学和干细胞生物学之间有趣的重叠已经被广泛地回顾了。衰老伴随着干细胞功能的逐渐下降，导致组织动态平衡和修复效率降低。组织的维持和再生依赖于干细胞，因此，由于衰老导致的任何数量或功能的丧失都可能对我们的再生能力产生深远的影响。因此，了解哺乳动物衰老相关干细胞功能障碍的基本分子途径，以及干细胞功能如何随年龄变化，包括自我更新受损和异常分化潜能，对再生医学和延长健康寿命的目标具有重要意义。躯体组织和器官的衰老伴随着再生能力的下降。通常，组织的动态平衡、再生和修复涉及新的实质细胞的连续出现和平行整合，这些细胞来自未分化的前体细胞。在成人中，间充质基质细胞含有组织特异性的多能干细胞，这种干细胞在全身都可以找到。多能基质祖细胞，也称为间充质干细胞(MSCs)，是一种与成人相关的组织特异性干细胞。MSC的概念似乎特别有趣，因为这种特殊类型的前体细胞可以产生多种不同的细胞类型，如骨、软骨、肌腱或脂肪前体细胞。间充质干细胞因其易于从多种组织中分离而成为众多研究人员关注的焦点。MSCs分化为多种细胞类型的能力使其成为许多新疗法的起点，特别是在组织工程学中。MSCs存在于一个复杂的三维网络中，该网络包括大量其他类型的细胞，如骨髓、造血干细胞(HSC)、脂肪细胞和内皮细胞，这些细胞共同嵌入不同的细胞外基质中，在这种混合中，MSC引导造血前体细胞分化为成熟的后代。骨髓间充质干细胞似乎还发挥着另一项相关功能，即维持血管完整性。与这些假设相联系，可以预见，在组织损伤和损伤时，间充质干细胞被激活和/或从血管周围的缝隙中释放出来，以支持伤口愈合和组织再生。尽管关于HSC的“衰老主题”已经进行了广泛的研究，不同的与年龄相关的变化和强大的分子机制可能被破译，但关于MSC在体内发生的衰老的明显细节还很少，这仅仅是因为我们仍然缺乏关于身体环境中内在特性的一致知识。然而，了解骨髓间充质干细胞老化的过程对于选择细胞疗法的捐赠者至关重要，这是成功治疗所必需的。细胞变化可分为三大类，包括：1)增殖率；2)分化能力；3)基因组稳定性。虽然许多工具已经被广泛地描述来评估MSCs中与年龄相关的转化，但衰老过程仍然是未知的，需要进一步的研究。本综述的目的是深入了解骨髓间充质干细胞、壁龛和组织之间的多方向相互作用，这些相互作用可能有助于衰老相关的变化。此外，基于MSC的治疗的重要方面将被考虑以突出可能损害安全和有效的临床应用的实际限制。
The interesting overlap between the biology of aging and the biology of stem cells has been reviewed extensively. Ageing is accompanied by a progressive decline in stem cell function, resulting in less effective tissue homeostasis and repair. Tissue maintenance and regeneration is dependent on stem cells and therefore, any loss in number or functionality due to aging will likely have a profound effect on our regenerative capacity. Therefore, understanding the basic molecular pathways of age-related stem cell dysfunction in mammals and how stem cell functionality changes with age, including impaired self-renewal and aberrant differentiation potential, have significant implications for regenerative medicine and the goal of extending ‘healthspan’. Aging of somatic tissues and organs comes along with a decline of regenerative capacity. Often, tissue homeostasis, regeneration and repair involve the consecutive emergence and parallel integration of new parenchymal cells, which descend from undifferentiated precursors. In adults, mesenchymal stromal cells contain tissue-specific multipotent stem cells, which can be found throughout the body. Multipotent stromal progenitor cells also known as Mesenchymal Stem Cells (MSCs) are pertinent tissue-specific stem cells in adult beings. The concept of MSC appears to be particularly interesting since this special type of precursor can bring forth a large spectrum of cell types as diverse as bone, cartilage, tendon, or fat precursor cells. MSCs are in the center of attention of many investigators due to easy isolation from many tissues. MSCs capability to differentiate into many cell types makes them a starting point of many new therapies, especially in tissue engineering. MSCs reside in a complex three-dimensional network, which comprises a plethora of other cell types such as, in the case of bone marrow, hematopoietic stem cells (HSC), adipocytes, and endothelial cells, altogether embedded in distinct extracellular matrix, and within this blend, MSC guide differentiation of hematopoietic precursor cells into mature progeny. MSCs appear to exert yet another pertinent function, namely maintaining blood vessel integrity. Linked to these presumptions, it can be envisaged that upon tissue damage and injury, MSCs are being activated and/or released from their perivascular niche, in order to support wound healing and tissue regeneration. While extensive research regarding the “Aging-topic” has been undertaken for HSC, and distinct age-related changes and potent molecular mechanisms could be deciphered, distinct details about MSC aging taking place in vivo is scarce, simply because we are still lacking consistent knowledge about intrinsic properties in a bodily setting. However, understanding the process of MSC-aging is crucial for selecting donors for cellular therapies, which is necessary for successful treatment. Cellular changes can be divided into three major groups that include alterations affecting: 1) proliferation rate 2) differentiation capability 3) genome stability. Although many tools have been extensively described to evaluate age-related transformations in MSCs, the aging-process still eludes and further investigations are required. The aim of this review is to take a deep insight into the multidirectional interactions among MSCs, niches and tissues that may contribute to the aged-associated changes. Moreover, significant aspects of MSC-based therapies will be considered to highlight practical limitations that might impair a safe and efficient clinical application.