衰老与死亡是每个人都必须面对的人生问题，我们无法避免死亡，但或许科学可以让我们更体面、更有质量地离开这个世界。“老而不衰”，年过八旬还能活动自如，可以说就是间充质干细胞缓解老化疗法的终极目标。
老化衰弱症（aging frailty）是一种随着年龄增长而症状增加的综合征，主要特征为身体和免疫功能下降，与炎症和干细胞功能障碍有关。研究发现，干细胞衰竭是导致衰弱的一个关键机制，基于干细胞的治疗策略也已进入临床研究阶段。
近年来，美国生物制药公司Longeveron LLC着力开发间充质干细胞治疗老化衰弱症的疗法，并于2017年4月和10月先后完成I期和II期临床研究，成绩喜人！
间充质干细胞具有强大的多向分化潜能，并具有抗炎、促进组织再生等作用，是能够抵抗老化衰弱的潜在干细胞类型！
在该疗法的I期临床研究中，15名受试者接受了不同剂量的间充质干细胞输注，输注后一个月观测受者的主要医学事件，在3个月和6个月时分别测定其炎症标志物和生理功能。结果显示，患者在接受间充质干细胞输注后1个月或6个月内，都未出现显著的免疫反应，TNF-α水平在6个月时显著降低。总体上，中、高剂量间充质干细胞输注组患者的炎症指标都出现显著好转，中剂量组患者的生命质量评估得分最高。
在II期临床研究中，30名老化衰弱症患者接受了间充质干细胞输注，其平均年龄近76岁。结果显示，接受输注的患者与未接受干预组患者相比，在生理表现、6分钟行走测试、女性性生活质量等方面都得到了显著改善，老化衰弱症相关炎症水平显著降低。I期和II期临床研究结果提示，间充质干细胞治疗老化衰弱症是安全且有效的！
令人振奋的是，10月18日，该间充质干细胞疗法获得了美国国立卫生研究院（NIH）的认可，并获批得到380万美金的创新研究资助。
Longeveron LLC创始人兼首席科学家Joshua Hare博士表示，接下来他们将用这笔资金开展更大规模的间充质干细胞治疗老年衰弱症临床试验，计划招募120名志愿者来进一步探究和验证该疗法的疗效，并且相信干细胞疗法将会对该疾病的治疗产生重大有益影响。
或许，我们现在还难以想象，当我们“七老八十”还可以如壮年一般旅行、运动，开启新的人生精彩，但这就是研究人员们正在努力实现的事，也是间充质干细胞的潜力所在，让我们拭目以待！
推荐阅读原文1：
Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty.
BACKGROUND:
Impaired endogenous stem cell repair capacity is hypothesized to be a biologic basis of frailty. Therapies that restore regenerative capacity may therefore be beneficial. This Phase 1 study evaluated the safety and potential efficacy of intravenous, allogeneic, human mesenchymal stem cell (allo-hMSC)-based therapy in patients with aging frailty.
METHODS:
In this nonrandomized, dose-escalation study, patients received a single intravenous infusion of allo-hMSCs: 20-million (n = 5), 100-million (n = 5), or 200-million cells (n = 5). The primary endpoint was incidence of any treatment-emergent serious adverse events measured at 1 month postinfusion. The secondary endpoints were functional efficacy domains and inflammatory biomarkers, measured at 3 and 6 months, respectively.
RESULTS:
There were no treatment-emergent serious adverse events at 1-month postinfusion or significant donor-specific immune reactions during the first 6 months. There was one death at 258 days postinfusion in the 200-million group. In all treatment groups, 6-minute walk distance increased at 3 months (p =0 .02) and 6 months (p =0 .001) and TNF-α levels decreased at 6 months (p < 0.0001). Overall, the 100-million dose showed the best improvement in all parameters, with the exception of TNF-α, which showed an improvement in both the 100- and 200-million groups (p =0 .0001 and p =0 .0001, respectively). The 100-million cell-dose group also showed significant improvements in the physical component of the SF-36 quality of life assessment at all time points relative to baseline.
CONCLUSIONS:
Allo-hMSCs are safe and immunologically tolerated in aging frailty patients. Improvements in functional and immunologic status suggest that ongoing clinical development of cell-based therapy is warranted for frailty.
推荐阅读原文2：
Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial.
BACKGROUND:
Aging frailty, characterized by decreased physical and immunological functioning, is associated with stem cell depletion. Human allogeneic mesenchymal stem cells (allo-hMSCs) exert immunomodulatory effects and promote tissue repair.
METHODS:
This is a randomized, double-blinded, dose-finding study of intravenous allo-hMSCs (100 or 200-million [M]) vs placebo delivered to patients (n = 30, mean age 75.5 ± 7.3) with frailty. The primary endpoint was incidence of treatment-emergent serious adverse events (TE-SAEs) at 1-month postinfusion. Secondary endpoints included physical performance, patient-reported outcomes, and immune markers of frailty measured at 6 months postinfusion.
RESULTS:
No therapy-related TE-SAEs occurred at 1 month. Physical performance improved preferentially in the 100M-group; immunologic improvement occurred in both the 100M- and 200M-groups. The 6-minute walk test, short physical performance exam, and forced expiratory volume in 1 second improved in the 100M-group (p = 0.01), not in the 200M- or placebo groups. The female sexual quality of life questionnaire improved in the 100M-group (p =0 .03). Serum TNF-α levels decreased in the 100M-group (p =0 .03). B cell intracellular TNF-α improved in both the 100M- (p <0 .0001) and 200M-groups (p = 0.002) as well as between groups compared to placebo (p =0 .003 and p =0 .039, respectively). Early and late activated T-cells were also reduced by MSC therapy.
CONCLUSION:
Intravenous allo-hMSCs were safe in individuals with aging frailty. Treated groups had remarkable improvements in physical performance measures and inflammatory biomarkers, both of which characterize the frailty syndrome. Given the excellent safety and efficacy profiles demonstrated in this study, larger clinical trials are warranted to establish the efficacy of hMSCs in this multisystem disorder.
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