Summary: This report examined the long-term course of a patient whose cutaneous amyloid deposits improved after adipose-derived stem cell (ADSC) administration, with follow-up of the same site five years later. The patient expressed high satisfaction with the reduction in cutaneous amyloid deposition that had progressed over several decades. However, other factors, including the natural course of the condition, are possible, so this case alone cannot establish an ADSC effect. Nevertheless, continued improvement after administration and reports of ADSC actions related to abnormal protein degradation suggested an association. The durability of effects is also considered an important question when considering possible applications not only to cutaneous amyloidosis but also to progressive neurodegenerative diseases.

Summary: This study evaluated neprilysin (NEP) activity in autologous adipose-derived stem cells (ADSCs) collected from patients with Alzheimer’s disease (AD), examining the potential for autologous transplantation therapy. ADSCs from seven participants, including five patients with AD, were used to measure positivity for the surface marker CD10, associated with neprilysin, an enzyme that degrades amyloid beta. ADSCs from patients with AD maintained extremely high CD10 positivity of 99.3–100.0%, confirming that neprilysin activity was sufficiently preserved. The findings indicate the potential applicability of ADSCs collected from AD patients’ own adipose tissue to amyloid beta degradation therapy through autologous transplantation, suggesting effectiveness as a safe treatment strategy minimizing rejection and infection risks.

Summary: This paper considered neurodegenerative diseases as disorders arising from abnormal protein accumulation (proteinopathies), and examined the possibility that adipose-derived stem cells (ADSCs) are involved in removing abnormal proteins. Reelin activity, which has been linked to phosphorylated tau, was assessed in ADSCs from patients with Alzheimer’s disease and was positive in all five cases. These findings suggested that ADSCs may have a broad role in removing abnormal proteins. The paper also discussed future research combining this possibility with homing, neuroprotective and anti-inflammatory actions.

Summary: This paper discussed the therapeutic potential and mechanisms of intravenous adipose-derived stem cell (ADSC) administration for amyotrophic lateral sclerosis (ALS). Alongside neural repair, secretion of cytokines and nerve growth factors, and homing to injured sites, it focused on the enzyme caspase-4, which may be involved in degrading the abnormal protein TDP-43 that accumulates in ALS. ELISA testing confirmed caspase-4 activity in ADSCs. The paper also stated that double-blind randomized controlled trials (RCTs) are necessary to test this hypothesis and expressed hope that it would contribute to future clinical research.

Summary: This report examined the effects on cognitive function of repeated intravenous administration of autologous adipose-derived stem cells (ADSCs).
Evaluation of nine participants with cognitive impairment found that the mean MoCA score improved from 10.3 to 19.6, with no deterioration in any participant. Amyloid PET performed in three patients with Alzheimer’s disease suggested reduced amyloid deposition in one case.
Regarding mechanism, the administered ADSCs were confirmed to express CD10 (neprilysin), which is involved in amyloid degradation, and a possible relationship with cognitive improvement was discussed. However, because the study was not a comparative trial with a control group, it stated that further verification of effectiveness is required.

Summary: This review surveyed stem cells used in regenerative medicine (iPS cells, ES cells and MSCs), focusing on mesenchymal stem cell (MSC) characteristics, current clinical applications and future prospects. In addition to the ability of MSCs to differentiate into multiple lineages, topics included tissue repair, anti-inflammatory actions, growth factor secretion and possible involvement with abnormal proteins such as amyloid. Bone marrow and dental pulp were noted as sources, while relatively minimally invasive collection and the ease of culturing a sufficient quantity of adipose-derived stem cells (ADSCs) were described as clinical advantages. The review also noted that homing, the tendency to accumulate at lesion sites after intravenous administration, may be important for clinical applications. It outlined the Japanese framework for stem cell treatment, including the Act on the Safety of Regenerative Medicine, review by a Certified Special Committee for Regenerative Medicine, submission of plans to the Ministry of Health, Labour and Welfare, and institutional ethical review, also organizing requirements for the medical care delivery system.

Summary: This pilot study examined whether repeated intravenous administration of autologous adipose-derived stem cells (ADSCs) for Parkinson’s disease could be performed safely in clinical practice. Three participants received five or six administrations at intervals of approximately one month. Evaluation included examinations by a neurologist, interviews with patients and caregivers, the Hoehn and Yahr scale and the MDS-UPDRS. No adverse events were observed during follow-up, from treatment initiation until six months after the final administration, and the report described improvement in MDS-UPDRS scores in all three participants. Acknowledging the small number of cases, it presented feasibility findings and basic knowledge for future research.

Summary: This report examined ADSC infusions in patients with ALS to assess safety and explore effectiveness. Six participants received three administrations of 4.3–8.7 × 10^7 ADSCs at intervals of one to two months. Examinations by several physicians, including a neurologist, and interviews with patients and caregivers were used for follow-up of up to three months after administration. Although no adverse events were observed, the report described one death due to disease progression. ALSFRS trajectories varied by case, with both maintenance and decline. The report explicitly noted the open-label design and lack of a control group, urging caution in judging effectiveness. It presented the possibility that repeated intravenous administration could be performed safely and that suggested maintenance or improvement of ALSFRS in some cases could provide a rationale for further trials.

Summary: This report described a patient with ALS who received autologous adipose-derived mesenchymal stem cells (ADSCs) and was followed over the long term. The patient was a 46-year-old man diagnosed with ALS in 2009 after symptoms including lower-limb weakness and choking when swallowing. His initial ALSFRS-R was 43, and symptoms progressed rapidly, with coughing during meals and conversation becoming problematic. Intravenous ADSC administration began in 2013, with six administrations in total. The report stated that the patient perceived less coughing during conversation and meals after administration and subsequently had no prominent dysphagia or dysarthria. ALSFRS-R reached a maximum of 45, and electromyography showed periods in which fasciculation potentials were not detected. The report explicitly noted that a single case cannot establish a causal relationship with treatment, while suggesting the possibility of safe administration and the need for further investigation.

Summary: Starting from the discussion that stem cells have neprilysin activity that degrades amyloid beta, this paper proposed a broader hypothesis: that they may have activity capable of “solubilizing and removing insoluble, deposited abnormal proteins.” It noted that cutaneous amyloid deposits and amyloid beta in the Alzheimer’s brain may not be identical, avoiding a simple equivalence. If confirmed, this property could have theoretical implications for amyloidosis not only of the skin but also of the heart, liver and kidneys, and for diseases characterized by abnormal protein deposition, such as ALS (TDP-43) and Parkinson’s disease (alpha-synuclein). The paper also mentioned possible verification methods, such as observing in vitro whether stem cells degrade insoluble substances.

Summary: This letter offered supplementary academic observations and clarified discussion points regarding a published report of intravenous autologous MSC administration in 13 patients with spinal cord injury. It focused on research methodology, including interpretation of a case series and desirable future verification, making clear that it did not establish the effectiveness of individual treatments.

Summary: This paper proposed, as a hypothesis, a treatment strategy involving intravenous autologous adipose-derived stem cell administration for Alzheimer’s disease. The central idea was that administered stem cells might secrete neprilysin in the brain and degrade and remove amyloid deposits. One supporting observation was a case in which cutaneous amyloid deposits regressed after stem cell administration, with neprilysin activity confirmed in the administered cells. The paper also discussed the possible simultaneous involvement of multiple mechanisms, including neural regeneration and repair, growth factor secretion, anti-inflammatory actions and angiogenesis. While noting that adipose-derived stem cells can be collected relatively minimally invasively and administered repeatedly by intravenous infusion, it concluded that effectiveness should be established through future verification.