Research

Our research team (theforem.org) conducts high quality clinical research published in good PubMed indexed journals. Some of our recent studies are listed below.

Publications

Autologous Mesenchymal Stem Cell Treatment is Consistently effective for the Treatment of Knee Osteoarthritis: The Results of a Systematic Review of Treatment and Comparison to a Placebo Group

Chadwick Prodromos, Susan Finkle, Tobias Rumschlag, and John Lotus

Abstract: Background: Numerous studies have used autologous mesenchymal stem cell injections (AMSCI) to treat osteoarthritis. We hypothesized that AMSCI is an effective osteoarthritis treatment with increasing effective at higher doses. Methods: We conducted a PubMed search for human clinical studies using AMSCI for the treatment of osteoarthritis (OA) and a second search for placebo arms of injectate OA treatment. Inclusion criteria included treatment outcomes ratings both pre-treatment and at least 6 months post-treatment.

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Administration of Autologous Mesenchymal Cells for the Treatment of Arthritis

Chadwick Prodromos, Tobias Rumschlag

Background: Injection of autologous mesenchymal stem cells (AMSCs) as stromal vascular fraction, culture expanded adipose derived stem cells, minimally manipulated fat graft, bone marrow aspirate or cultured bone marrow MSCs, for osteo- and inflammatory arthritis have shown good clinical efficacy in many studies. Questions have been raised as to their safety despite no evidence known to us that they are unsafe when used this way. We hypothesized that AMSC injections are completely safe for the treatment of arthritis.

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Autologous Biologic Treatment with Fat, Bone Marrow Aspirate and Platelet Rich Plasma Is an Effective Alternative to Total Knee Arthroplasty for Patients with Moderate Knee Arthrosis

Chadwick Prodromos, and Susan Finkle

Background: Osteoarthrosis (OA) of the knee afficts millions worldwide. Total Knee Arthroplasty (TKA) is common, but associated with substantial cost and morbidity. Prior studies of intra-articular injection of fat, bone marrow aspirate (BMA), and platelet rich plasma (PRP) have shown clinical benefit. We hypothesized that injection of autologous adipose tissue, BMA, and PRP would provide significant benefit for patients with moderate knee OA resulting in avoidance of total knee arthroplasty (TKA) in most, with discontinuance of NSAIDs and other drugs.

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Treatment of Rotator Cuff Tears with platelet rich plasma: a prospective study with 2 year follow-up

Chadwick C Prodromos, Susan Finkle, Alexandra Prodromos, Jasmine Li Chen, Aron Schwartz, Lucas Wathen

Background: Surgical treatment of full thickness rotator cuff (RC) tears is associated with generally good results. There is no consensus regarding treatment of partial thickness tears that fail activity modification and physical therapy. Corticosteroid injections are sometimes used but have been associated with tendon damage. Platelet rich plasma (PRP) however has been shown to enhance connective tissue healing. We hypothesized that dual PRP injection into the rotator cuff insertion as well as the area of the tendon proximal to the insertion would be safe and would result in good clinical outcomes without surgery, that the effects would last out to two years, and that results would be better with lesser tendon damage.

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Presentations

The Aggregated Data from Normal Saline Placebo Arms of Hyaluronic Acid and Other Knee Injection Studies For OA Can Be Used as a Control Group for Single-Armed Knee Injection Studies.

Chadwick Prodromos, John Lotus, and Susan Finkle

2021 European Society for Sports Traumatology, Knee Surgery and Arthroscopy Presentation

PRP Injection of the Arthritic Glenohumeral Joint is Safe, Effective, and Avoids Joint Replacement in Many Patients at 2-8 year Follow-Up

J. Sharan, C. Prodromos, S. Finkle, A. Barmada, A. Schwartz, J. Delapaz, N. Band

Purpose: Platelet Rich Plasma (PRP) injection has been shown to benefit knee osteoarthritis (OA). We are unaware of any published studies evaluating efficacy for glenohumeral shoulder OA. We hypothesized that PRP would be safe, would improve glenohumeral OA, and would result in joint replacement avoidance in many patients.

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PRP Injection Resulted in Joint Replacement Avoidance in 568 OA Knees at 3 - 7 Year Follow Up, Even Bone on Bone

J. Sharan, C. Prodromos, S. Finkle, A. Barmada, K. Ralston, K. Bruch, K. Phelan, B. Schuler

Purpose: Most knee PRP studies report only short term results and fail to assess total knee replacement (TKR) avoidance/joint survivorship as an outcome. We wished to evaluate the efficacy of PRP at 3 year follow up with particular attention to TKR avoidance.

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The Grashey True Shoulder AP X-Ray Accurately Reflects Glenohumeral Joints Space and Predicts PRP Efficacy, The Traditional AP Does Neither

A. Barmada, C. Prodromos, J. Sharan, S. Finkle, J. Delapaz, A. Schwartz, A. Dawes, N. Band

Purpose: To demonstrate that the shoulder AP view radiograph does not accurately reflect true glenohumeral (GH) joint space narrowing when compared to the Grashey view.

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Pre-Publication Abstracts

Intrathecal Mesenchymal Stem Cell Injection for the Treatment of Neurologic Disorders and Injury is Extremely Safe: A Systematic Review

Chadwick C. Prodromos, Amir Barmada, Joshua Sharan

Purpose: To explore the safety of intrathecal injection of mesenchymal stem cells

Methods: We performed a literature search for serious adverse events related to intrathecal injection of mesenchymal stem cells (MSCs). PubMed and Google Scholar were used to find relevant studies. We performed disease specific searches that included: Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), Autism, Cerebral Palsy (CP), Parkinson’s disease, Spinal Cord Injury (SCI), and Traumatic Brain Injury (TBI). Specifically looking for clinical trials, we cross referenced these diseases with the term “Mesenchymal stem cell.” In addition, we performed a search using the terms: “Mesenchymal Stem Cell” and “serious adverse event”

We excluded articles in which hematopoietic stem cells or genetically modified MSCs were used. We excluded articles in which MSCs were combined with alternative medications or surgery. In addition, we excluded pre-clinical studies. Adverse events resulting from standard medical procedures but not from the stem cells themselves were excluded. We only included studies with intrathecal injection as the delivery route.

Results: A total of 252 articles were identified using the search criteria. 212 articles were excluded based on the exclusion criteria leaving 40 articles for analysis. Thousands of patients were treated and only one related SAE was identified, which was transient seizures and encephalopathy.

Conclusions: Intrathecal injection of MSCs is extremely safe and should be offered freely where evidence of efficacy exists. After thousands of infusions from forty papers only one SAE occurred which resolved without sequela. Notably, no infections or tumors occurred. Properly performed intrathecal MSC injection is one of the safest treatment paradigms in existence, with a far lower SAE incidence than the immunosuppressive drugs which often are used for treatment of disorders for which MSCs have been shown to have efficacy.

Intravenous Injection of Mesenchymal Stem Cells Is Very Safe As Treatment For a Wide Variety of Disorders: A Systematic Review

Chadwick C. Prodromos, Amir Barmada, Joshua Sharan

Purpose: To identify and determine the frequency of serious adverse events after intravenous infusion of mesenchymal stem cells (MSCs).

Methods: PubMed and Google Scholar were used to search the scientific literature for serious adverse events related to intravenous infusion of mesenchymal stem cells (MSCs). Disease specific searches included: Multiple Sclerosis (MS), Rheumatoid Arthritis (RA), Amyotrophic Lateral Sclerosis (ALS), Ankylosing Spondylitis, Frailty, Autism, Cerebral Palsy (CP), Diabetes, Idiopathic Pulmonary Fibrosis (IPF), Chronic Obstructive Pulmonary Disease (COPD), Crohn’s Disease, Ulcerative Colitis, Lupus, Parkinson’s disease, Scleroderma, Spinal Cord Injury (SCI), and Traumatic Brain Injury (TBI). Specifically looking for clinical trials, we cross referenced these diseases with the following terms: “Mesenchymal stem cell”, or “Stem cell.” In addition, we performed searches using “Human mesenchymal stem cell” and “serious adverse event”

We excluded articles in which hematopoietic stem cells or genetically modified MSCs were used. We excluded articles in which MSCs were combined with medications or surgery. In addition, we excluded pre clinical studies and studies that did not define the nature of the SAE. Patients with preexisting multi system organ failure or malignancies were excluded. We only included studies with intravenous infusion as the delivery route and only noted SAEs that were directly related to the MSCs.

Results: A total number of 664 articles were identified using the initial search criteria. A total of 547 articles were excluded based on our exclusion criteria leaving 117 articles for inclusion in the safety review. The only SAEs were two upper extremity thromboembolisms from the same clinic in China, both in patients with renal disease, both of which resolved without sequelae and without pulmonary embolism.

Conclusion: Intravenous injection of MSCs is extremely safe and should be offered freely where evidence of efficacy exists. After thousands of reported injections the only SAEs causally related to i.v. MSC injection are two upper extremity thromboses without sequelae. Notably, no infections or tumors have been identified after iv MSC injection. I.V MSC injection is one of the safest treatment paradigms in existence, with a far lower SAE incidence than the immunosuppressive drugs which often are used for treatment of disorders for which MSCs have been shown to have efficacy.

First Report in a Human of Successful Treatment of Asthma with Mesenchymal Stem Cells: Phase 1 Clinical Trial with Review of Literature

Chadwick C. Prodromos, Joshua Sharan, Amir Barmada

IntroductionAsthma is a heterogeneous disorder characterized by chronic airway inflammation resulting in obstructive pulmonary symptoms. In preclinical studies, MSCs have demonstrated the ability to ameliorate symptoms and immunologic pathways seen in asthma. Due to the known relationship between asthma and a hyper-responsive immune cascade, we hypothesize that mesenchymal stem cells (MSCs) could be an effective treatment option for patients with asthma due to their significant immunomodulatory properties.

Objective: We present the initial results for the first patient enrolled in a phase 1 clinical trial (Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cell Intravenous Infusion for Pulmonary Diseases)

Case Report: A 68-year-old male with a longstanding history of asthma presented requesting mesenchymal stem cell treatment for his persistent asthma symptoms. Cultured umbilical cord derived mesenchymal stem cells (UC-MSCs) were infused intravenously at a dose of 100 million cells over a period of 40 minutes. Post-treatment follow up was performed after two months. The patient had no adverse events or complications related to treatment. In the two months post treatment, his usage of rescue inhaler decreased from twice weekly to one to two times in two months, a 90% reduction. In addition, he had a 70% reduction in nebulizer usage.

Conclusion: We report the first case of MSCs significantly and safely improving asthma clinical symptoms in a human. Additionally, an extensive literature review provided several plausible mechanisms by which MSCs can ameliorate immune hyperstimulation associated with asthma.

First Report of Successful Treatment of Spinal Arthritis with Mesenchymal Stem Cells: Phase 1 Clinical Trial with Review of Literature

Chadwick C. Prodromos, Joshua Sharan, Amir Barmada

Introduction: Lumbar back pain is a multifactorial condition which is frequently caused by discogenic disease or facet joint disease, which have frequently been shown to occur concomitantly. Due to the immunomodulatory and anti-inflammatory properties of mesenchymal stem cells (MSCs), we hypothesized that they would be efficacious in the treatment of spinal arthritis. Multiple studies have demonstrated that intradiscal injections of MSCs can be efficacious, however; this has not been without risk as multiple studies have described adverse events including discitis, osteomyelitis, epidural abscess, cauda equina syndrome and inducing disc herniation. Therefore, we believe that treating simultaneous discogenic and facet joint disease can be done by directly injecting the facet joint along with epidural injection, which would saturate the disc with beneficial cytokines and immunomodulators.

Objective: We present the initial results for the first patient enrolled in a phase 1 clinical trial (Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for Osteoarthritis)

Case Report: A 47-year-old male presented with complaints of severe chronic lower back pain associated with frequent intense lumbar paraspinal spasms. His symptoms were interfering with his activities of daily living and resulted in reduced quality of life. Radiographs were used to confirm the diagnosis of spinal arthritis and MRI revealed significant degenerative disc disease and facet joint disease throughout the lumbar and lower thoracic spinal segments. The decision was made to treat the patient with UC-MSCs. The cells were infused intravenously and injected into the facet joints and epidural space at a cell count of 87x10^6, 8x10^6 and 5x10^6, respectively. One month post treatment, the patient had no adverse events or complications related to the treatment. The patient states that his severe paraspinal spasms and lumbar pain have completely resolved. The improvement in symptoms was associated with a significant increase in quality of life.

Conclusion:  We report the first case of MSCs significantly and safely improving lumbar pain and spasm after facet joint and epidural injection. Literature review provided several potential mechanisms by which MSCs can reduce lumbar back pain.

 

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