Osteoarthritis (OA) is a degenerative cartilage disease that is characterized by a local inflammatory reaction. Consequently, many studies have been performed to identify suitable prevention and treatment interventions. In recent years, both arthroscopic microfracture (AM) and stem cell therapy have been used clinically to treat OA. This study aimed to evaluate the clinical effects of AM in the presence and absence of a stromal vascular fraction (SVF) injection in the management of patients with OA. Thirty patients with grade 2 or 3 (Lawrence scale) OA of the knee participated in this study. Placebo group patients (n = 15) received AM alone; treatment group patients (n = 15) received AM and an adipose tissue-derived SVF injection. The SVF was suspended in platelet-rich plasma (PRP) before injection into the joint. Patient groups were monitored and scored with the Western Ontario and McMaster Universities Arthritis Index (WOMAC), Lysholm, Visual Analog Pain Scale (VAS), and modified Outerbridge classifications before treatment and at 6, 12, and 18 months post-treatment. Bone marrow edema was also assessed at these time points. Patients were evaluated for knee activity (joint motion amplitude) and adverse effects relating to surgery and stem cell injection. Treatment efficacy was significantly different between placebo and treatment groups. All treatment group patients had significantly reduced pain and WOMAC scores, and increased Lysholm and VAS scores compared with the placebo group. These findings suggest that the SVF/PRP injection efficiently improved OA for 18 months after treatment. This study will be continuously monitored for additional 24 months. Stem Cells Translational Medicine 2017;6:187-195.

https://stemcellsjournals.onlinelibrary.wiley.com/doi/epdf/10.5966/sctm.2016-0023

Comparative Clinical Observation of Arthroscopic Microfracture in the Presence and Absence of a Stromal Vascular Fraction Injection for Osteoarthritis

Mesenchymal stromal cells (MSCs) can differentiate into multiple tissues. Preclinical studies have shown that MSC-based therapy is a potential new treatment approach for ischemic stroke. These results support the urgent need for further studies of MSC transplantation in the treatment of ischemic stroke in humans. Here, we develop a prospective, randomized, controlled, observer-blinded phase II trial to assess the clinical safety, feasibility, and therapeutic mechanisms of allogenic bone marrow-derived MSCs (BM-MSCs) by intrathecal infusion in the treatment of patients with cerebral infarction within the middle cerebral artery and with a National Institutes of Health Stroke Scale (NIHSS) score from 15 to 25. Sample size calculation has determined that a patient population of 118, with ischemic stroke between 30 and 90 days following onset, will be randomly divided into experimental (n = 59) and control (n = 59) groups. Then eligible patients will receive four intrathecal infusions of allogenic BM-MSCs (1 × 106 cells/kg body weight) once a week. All patients have detailed functional assessments and magnetic resonance imaging prior to cell infusion and at intervals up to 1 year after. The primary outcome is the score on the modified Rankin Scale at 90 days after treatment, and the second outcomes include multiple indicators of safety and feasibility. And this trial has been registered as ChiCTR-INR-16008908 (25 July 2016).

Intrathecal Injection of Allogenic Bone Marrow-Derived Mesenchymal Stromal Cells in Treatment of Patients with Severe Ischemic Stroke: Study Protocol for a Randomized Controlled Observer-Blinded Trial

Review question/objective

The objective of this review is to present the best available evidence related to allied health therapy in the symptomatic management of progressive supranuclear palsy. More specifically, the review question to be addressed is:
•What are effective physiotherapy, occupational therapy and speech therapy techniques used in the symptomatic management of progressive supranuclear palsy?

Inclusion criteria

Types of participants

This review will consider all studies that include participants with a diagnosis of probable progressive supranuclear palsy according to The National Institute of Neurological Disorders and Stroke and the Society for progressive supranuclear palsy criteria. In the absence of studies with a diagnosis of probable progressive supranuclear palsy, participants with a diagnosis of possible progressive supranuclear palsy will also be considered. 
If the diagnosis method is not provided, efforts will be made to contact the authors to clarify if the diagnosis was made according to The National Institute of Neurological Disorders and Stroke and the Society for progressive supranuclear palsy. Participants will need to be over the age of 40 years, as age of onset under the age of 40 years is not supportive of a diagnosis of progressive supranuclear palsy
Only participants with a primary diagnosis of progressive supranuclear palsy will be considered. Exclusion criteria include additional conditions not usually associated with progressive supranuclear palsy likely to affect mobility, vision, swallowing, communication or cognition. Examples include congenital conditions, structural abnormalities, or cancer in particular regions of the body (oral, laryngeal, pharyngeal or esophageal cancer affecting swallowing).
Participants across different stages of the disease may benefit from physiotherapy, occupational therapy and speech therapy, therefore all participants will be included regardless of length of time since diagnosis. Participants across all types of settings including community, hospital or residential care will be considered.

Types of intervention(s)

The scope of existing literature for the symptomatic management of progressive supranuclear palsy is relatively limited. This review will consider studies that evaluate any Allied Health Therapy that addresses mobility, vision, swallowing, communication or cognitive difficulties experienced by people with progressive supranuclear palsy as per Table 3. More specifically, physiotherapy, occupational therapy and TRUNCATED AT 350 WORDS

/pdf/effectiveness-of-allied-health-therapy-in-the-symptomatic-1j6c92dmr2.pdf

Effectiveness of allied health therapy in the symptomatic management of progressive supranuclear palsy: a systematic review.

Adipose-derived stem cells (ADSCs) are the most commonly used type of mesenchymal stem cell (MSC) in the clinic. ADSCs have some advantages in transplantation compared with MSCs from bone marrow and umbilical cord blood. ADSCs produce important growth factors for wound healing, modulate the immune system, decrease inflammation, and home to injured tissues. In particular, ADSC extraction from adipose tissue is a simple procedure with minimum invasiveness. Therefore, ADSCs have been evaluated in clinical trials and used in the treatment of many diseases. To date, ADSC transplantation has been approved in some countries to treat medical complications such as perianal pistula and osteoarthritis. This review provides an overview of the applications and future challenges of the use of ADSCs in clinical settings.

/pdf/adipose-stem-cells-in-the-clinic-5a300esw09.pdf

Adipose stem cells in the clinic

Cell replacement therapy with graft transplantation has been tested as a disease-modifying treatment in neurodegenerative diseases characterized by the damage of a predominant cell type, such as substantia nigra dopaminergic neurons in Parkinson's disease (PD) or striatal medium spiny projection neurons in Huntington's disease (HD). The results of these trials are mixed with success in preclinical and pilot open-label trials, which were not consistently reproduced in randomized controlled trials. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) molecular imaging and functional magnetic resonance imaging allow the graft survival, and its relationship with the host tissues to be studied in vivo. In PD, PET with [18F]DOPA showed that graft survival does not necessarily correlate with the clinical improvement and PD patients with worse outcome had lower binding in the ventral striatum and a high serotonin ([11C]DASB PET) to dopamine ([18F]DOPA PET) ratio in the grafted neurons. In HD, PET with [11C]PK11195 showed the graft survival and the clinical responses may be related to the reactive activation of the host inflammatory/immune system. Findings from these studies have been used to refine study protocols and patient selection in current clinical trials, which includes identifying suitable candidates for transplantation using imaging markers and employing multiple and/or novel PET tracers to better assess graft functions and inflammatory responses to grafts.

Imaging Transplantation in Movement Disorders.

Progressive supranuclear palsy is a relentlessly progressive neurodegenerative disorder and is clinically characterized by parkinsonism. Adipose tissue-derived mesenchymal stem cells have recently demonstrated the possibility of treating neurological disorders. Therefore, autologous adipose tissue-derived mesenchymal stem cells transplantation can be an alternative method for treating progressive supranuclear palsy. This study was approved by the Korea Food and Drug Administration through the Emergency Use Investigational New Drug Application. A 71-year-old Asian man from South Korea with progressive supranuclear palsy was treated with five intravenous infusions (each time 2×108 cells) and four intrathecal infusions (each time 5×107 cells) with autologous adipose tissue-derived mesenchymal stem cells expanded under good manufacturing practice conditions. Clinical examinations were performed immediately before treatment and throughout the six months of follow-up. The tests included: 1) Progressive Supranuclear Palsy Rating Scale; 2) Berg Balance Scale; 3) Korean Mini Mental State Examination; 4) Modified Barthel Index; 5) grip strength; 6) Box and Block Test; and 7) Nine-Hole Peg Test. The Progressive Supranuclear Palsy Rating Scale results gradually decreased, and the clinical rating scale scores of the Berg Balance Scale, Korean Mini Mental State Examination, and Modified Barthel Index gradually increased. Grip strength was maintained. Performance in the Box and Block Test and Nine-Hole Peg Test improved after adipose tissue-derived mesenchymal stem cells treatment compared to baseline throughout the six months of follow-up. Except for the intermittent mild fever and transient elevated blood pressure, the treatment of our patient with progressive supranuclear palsy with autologous adipose tissue-derived mesenchymal stem cells showed no significant adverse events, and delayed the progression of neurological deficits by achieving functional improvement in the follow-up period. These results are encouraging and hopeful for further studies in patients with progressive supranuclear palsy using autologous adipose tissue-derived mesenchymal stem cells as a safe and effective therapy. This case report is the first known study of adipose tissue-derived mesenchymal stem cells safely delaying the progression of progressive supranuclear palsy with functional improvement during the follow-up period.

/pdf/treatment-of-progressive-supranuclear-palsy-with-autologous-4m5lbi4zda.pdf

Soo Won Choi

Papers

Treatment of progressive supranuclear palsy with autologous adipose tissue-derived mesenchymal stem cells: a case report