Stem cell therapy has emerged as a groundbreaking treatment approach, particularly for type 1 diabetes, where the autoimmune destruction of beta cells necessitates regenerative strategies to restore insulin production. This article focuses on the recent medical milestone in which autologous stem cell therapy led to insulin independence in a type 1 diabetes patient. This article explores the role of stem cell therapy in reversing diabetes, focusing on the recent medical milestone in which stem cell therapy successfully reversed diabetes in a patient. Stem cells, particularly induced pluripotent stem cells, are used to regenerate pancreatic cells that produce insulin, thereby potentially eliminating the need for insulin injections. The study highlights both the promises and challenges of using stem cell therapy for diabetes including concerns about durability of the response, safety and long-term functionality of generated beta cells. Clinical trials and the ethical considerations of using stem cells are also discussed, along with future directions for stem cell-based diabetes therapies.

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Objectives: To evaluate the efficacy of repeated intravenous doses of 10   106/kg allo-hMSCs in improving motor symptoms in patients with PD (PwP). Methods: In this phase 2, randomized, placebo-controlled trial (November 2020–July 2023), mild-to-moderate PwP received either three allo-hMSC infusions, one placebo followed by two allo-hMSC infusions, or three placebo infusions at 18-week intervals. Follow-up lasted 88 weeks. The primary outcome was a >70%posterior probability (PP) of a difference in the proportion of participants with ≥5-point improvement in OFF-medication Movement Disorder Society Sponsored Revision of the Unified Parkinson’s Disease Rating Scale-Part III (MDS-UPDRS-III) at week 62. Bayesian analysis was conducted using R v4.2.0.

Results: Forty-five PwP were enrolled. A larger proportion of subjects achieved a ≥5-point improvement in MDS-UPDRS-III in the three-infusion arm compared with placebo at week 62 (mean difference [MD]: 5.0%, PP = 93.7%), translating to a 16.9-point improvement in MDS-UPDRS-III in the three-infusion arm compared with a 14.6-point improvement in the placebo arm. Conversely, fewer subjects in the two-infusion arm compared with placebo showed ≥5-point improvement at week 62 (MD: –62.4%, PP ≥ 99.9%), translating to only a 3.9-point improvement in MDS-UPDRS-III in the two-infusion arm. However, improvement in MDS-UPDRS-III was seen across all treatment arms. Adverse events were mild and transient.

Conclusions: Three infusions of 10   106 allo-hMSCs/kg improved motor function in mild-to-moderate PwP, while two infusions showed less improvement than placebo. To address this discrepancy, future studies should conduct functional potency assays to understand batch-to-batch variability affecting clinical efficacy.

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Tendon-bone insertion injuries such as rotator cuff and anterior cruciate ligament injuries are currently highly common and severe. The key method of treating this kind of injury is the reconstruction operation. The success of this reconstructive process depends on the ability of the graft to incorporate into the bone. Recently, there has been substantial discussion about how to enhance the integration of tendon and bone through biological methods. Stem cells like bone marrow mesenchymal stem cells (MSCs), tendon stem/progenitor cells, synovium-derived MSCs, adipose-derived stem cells, or periosteum-derived periosteal stem cells can self-regenerate and potentially differentiate into different cell types, which have been widely used in tissue repair and regeneration. Thus, we concentrate in this review on the current circumstances of tendon-bone healing using stem cell therapy.

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Despite relatively good results of current symptomatictreatments for rotator cuff disease, there has been an unmetneed for fundamental treatments to halt or reverse the progressof disease. The purpose of this study was to assess the safety andefficacy of intratendinous injection of autologous adiposetissue-derived mesenchymal stem cells (AD MSCs) in patientswith rotator cuff disease. The first part of the study consists ofthree dose-escalation cohorts; the low- (1.0 × 10 cells), mid- (5.0× 10), and high-dose (1.0 × 10) groups with three patients eachfor the evaluation of the safety and tolerability. The second partincluded nine patients receiving the high-dose for theevaluation of the exploratory efficacy. The primary outcomeswere the safety and the shoulder pain and disability index(SPADI). Secondary outcomes included clinical, radiological, andarthroscopic evaluations. Twenty patients were enrolled in thestudy, and two patients were excluded. Intratendinous injectionof AD MSCs was not associated with adverse events. Itsignificantly decreased the SPADI scores by 80% and 77% in themid- and high-dose groups, respectively. Shoulder pain wassignificantly alleviated by 71% in the high-dose group. Magneticresonance imaging examination showed that volume of thebursal-side defect significantly decreased by 90% in the high-dose group. Arthroscopic examination demonstrated thatvolume of the articular- and bursal-side defects decreased by83% and 90% in the mid- and high-dose groups, respectively.Intratendinous injection of autologous AD MSCs in patient witha partial-thickness rotator cuff tear did not cause adverse events,but improved shoulder function, and relieved pain throughregeneration of rotator cuff tendon.

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These movements are difficult for people with Parkinson’s disease. The disorder eats away at brain cells—called dopamine neurons—that control movement and emotion. Symptoms begin with tremors. Then muscles lock up. Eventually, the disease makes walking and sleeping difficult. Thinking gets harder, and as neurons die, people lose their concentration and memory. 

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Chronic neuropathic pain is estimated to be on the rise, particularly with the expected increase in patients with diabetes within the US. Diabetic and nondiabetic patients were surveyed for sick days from
work due to neuropathic pain; approximately two-thirds of these patients were found to consistently be taking days from work, and only one-fifth of those were satisfied with their current therapy.8,24 Unlike nociceptive pain (tissue injury induced), neuropathic pain is specific to injury of either the central or peripheral nervous system and can be a combination of both. For this reason, several diseases manifest with neuropathy including SCI, stroke, multiple sclerosis, diabetes, infectious related, nutrient deficient,
immune related, and oncological. Interestingly, adjuvant therapies for these disorders including chemotherapy and radiation therapy can also lead to chronic neuropathy. Treatments have largely depended on anticonvulsants and antidepressants because of their analgesic effects; however, the nature of neuropathic pain is its chronicity and as such often becomes recalcitrant to these pharmacological strategies. Intractable neuropathic pain has gained increasing awareness due to its prevalence and the technological advancements in surgical neuromodulation. Electrical stimulation via spinal cord, peripheral nerve, and deep brain targeting has begun to show some early efficacy. 18 To date, chronic neuropathic pain is largely considered a heterogeneous pain syndrome that remains with limited efficacious treatment modalities. Also, there is no treatment strategy that is effective for pain management while promoting nervous system repair.

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ABSTRACT

Mesenchymal stem cells (MSCs) are very attractive candidates in cell-based strategies that target
inflammatory diseases. Preclinical animal studies and many clinical trials have demonstrated that
human MSCs can be safely administered and that they modify the inflammatory process in the
targeted injured tissue. Our laboratory developed a novel method that optimizes the anti-inflammatory effects of MSCs. We termed the cells prepared by this method MSC2. In this study, we
determined the effects of MSC2-based therapies on an inflammation-linked painful diabetic peripheral neuropathy (pDPN) mouse model. Streptozotocin-induced diabetic mice were treated with
conventionally prepared MSCs, MSC2, or vehicle at three specific time points. Prior to each treatment, responses to radiant heat (Hargreaves) and mechanical stimuli (von Frey) were measured.
Blood serum from each animal was collected at the end of the study to compare levels of inflammatory markers between the treatment groups. We observed that MSC2-treated mice had significant
improvement in behavioral assays compared with the vehicle and MSC groups, and moreover these
responses did not differ from the observations seen in the healthy wild-type control group. Mice
treated with conventional MSCs showed significant improvement in the radiant heat assay, but not
in the von Frey test. Additionally, mice treated with MSC2 had decreased serum levels in many
proinflammatory cytokines compared with the values measured in the MSC- or vehicle-treated
groups. These findings indicate that MSC2-based therapy is a new anti-inflammatory treatment to
consider in the management of pDPN. STEM CELLS TRANSLATIONAL MEDICINE 2012;1:
557–565

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Objective:

Mesenchymal stem cells (MSCs) have been shown in animal models to attenuate
chronic neuropathic pain. This preliminary study investigated if: i) injections of autologous
MSCs can reduce human neuropathic pain and ii) evaluate the safety of the procedure.

Methods:

Ten subjects with symptoms of neuropathic trigeminal pain underwent liposuction.
The lipoaspirate was digested with collagenase and washed with saline three times. Following
centrifugation, the stromal vascular fraction was resuspended in saline, and then transferred to
syringes for local injections into the pain fields. Outcome measures at 6 months assessed reduction in: i) pain intensity measured by standard numerical rating scale from 0–10 and ii) daily
dosage requirements of antineuropathic pain medication.

Results:

Subjects were all female (mean age 55.3 years ± standard deviation [SD] 14.67; range
27–80 years) with pain symptoms lasting from 4 months to 6 years and 5 months. Lipoaspirate
collection ranged from 102–214 g with total cell numbers injected from 33 million to 162 million
cells. Cell viability was 62%–91%. There were no systemic or local tissue side effects from the
stem cell therapy (n=41 oral and facial injection sites). Clinical pain outcomes showed that at 6
months, 5/9 subjects had reduced both pain intensity scores and use of antineuropathic medication. The mean pain score pre-treatment was 7.5 (SD 1.58) and at 6 months had decreased to 4.3
(SD 3.28), P=0.018, Wilcoxon signed-rank test. Antineuropathic pain medication use showed
5/9 subjects reduced their need for medication (gabapentin, P=0.053, Student’s t-test).
Conclusion: This preliminary open-labeled study showed autologous administration of stem
cells for neuropathic trigeminal pain significantly reduced pain intensity at 6 months and is a
safe and well tolerated intervention.

Keywords: adipose, stem cells, neuropathic, orofacial, trigeminal

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