Cell-therapy for Parkinson’s disease: a systematic review and meta-analysis


Background: Cell-based strategies focusing on replacement or protection of dopaminergic neurons have been considered as a potential approach to treat Parkinson’s disease (PD) for decades. However, despite promising preclinical results, clinical trials on cell-therapy for PD reported mixed outcomes and a thorough synthesis of these findings is lacking. We performed a systematic review and meta-analysis to evaluate cell-therapy for PD patients.

Methods: We systematically identified all clinical trials investigating cell- or tissue-based therapies for PD published before July 2023. Out of those, studies reporting transplantation of homogenous cells (containing one cell type) were included in meta-analysis. The mean difference or standardized mean difference in quantitative neurological scale scores before and after cell-therapy was analyzed to evaluate treatment effects.

Results: The systematic literature search revealed 106 articles. Eleven studies reporting data from 11 independent trials (210 patients) were eligible for meta-analysis. Disease severity and motor function evaluation indicated beneficial effects of homogenous cell-therapy in the ‘of’ state at 3-, 6-, 12-, or 24-month follow-ups, and for motor function even after 36 months. Most of the patients were levodopa responders (61.6–100% in different follow-ups). Cell-therapy was also effective in improving the daily living activities in the ‘of’ state of PD patients. Cells from diverse sources were used and multiple transplantation modes were applied. Autografts did not improve functional outcomes, while allografts exhibited beneficial effects. Encouragingly, both transplantation into basal ganglia and to areas
outside the basal ganglia were effective to reduce disease severity. Some trials reported adverse events potentially related to the surgical procedure. One confirmed and four possible cases of graft-induced dyskinesia were reported in two trials included in this meta-analysis.

Conclusions: This meta-analysis provides preliminary evidence for the beneficial effects of homogenous cell-therapy for PD, potentially to the levodopa responders. Allogeneic cells were superior to autologous cells, and the effective transplantation sites are not limited to the basal ganglia.

PROSPERO registration number: CRD42022369760

Keywords Parkinson’s disease, Cell-therapy, Homogenous cell, Transplantation, Meta-analysis

The potential use of mesenchymal stem cells and their exosomes in Parkinson’s disease treatment


Parkinson’s disease (PD) is the second most predominant neurodegenerative disease worldwide. It is recognized clinically by severe complications in motor function caused by progressive degeneration of dopaminergic neurons (DAn) and dopamine depletion. As the current standard of treatment is focused on alleviating symptoms through Levodopa, developing neuroprotective techniques is critical for adopting a more pathology-oriented therapeutic approach. Regenerative cell therapy has provided us with an unrivaled platform for evaluating potentially effective novel methods for treating neurodegenerative illnesses over the last two decades. Mesenchymal stem cells (MSCs)
are most promising, as they can differentiate into dopaminergic neurons and produce neurotrophic substances. The precise process by which stem cells repair neuronal injury is unknown, and MSC-derived exosomes are suggested to be responsible for a significant portion of such effects. The present review discusses the application of mesenchymal stem cells and MSC-derived exosomes in PD treatment.

Keywords: Mesenchymal stem cell, Exosome, Parkinson’s disease, Therapeutic application

Clinical efficacy and safety of stem cell therapy for knee osteoarthritis


Background: We performed a meta-analysis of the efficacy and safety of stem cell therapy as a clinical treatment of knee osteoarthritis. This meta-analysis is expected to provide evidence of the efficacy of stem cell therapy, which is currently controversial, as a conservative treatment for knee osteoarthritis.
Methods: An online search for relevant articles was conducted in the PubMed, EMBASE, and Cochrane Library databases. The search terms were “stem cells” and “osteoarthritis.” We conducted a quality assessment of the included articles and extracted the following indicators: Visual Analogue Scale (VAS) score, Subjective International Knee Documentation Committee (IKDC) score, Western Ontario and McMaster Universities (WOMAC) subscales, and adverse events. The RevMan5.3 software was used for
determining effect sizes.

Results: Nine randomized controlled trials involving 339 patients were included. VAS score and IKDC score from baseline to 24 months were improved in the stem cell therapy group compared to those in the control group. However, no significant difference was observed between the 2 groups in IKDC score changes from baseline to 6 and 12 months, as well as in WOMAC-Pain, WOMACStiffness, and WOMAC-Physical Function score changes at each visit point.

Conclusion: Stem cell therapy is certainly superior to traditional treatments in the conservative treatment of KOA; it considerably reduces pain with no obvious additional side effects.

Abbreviations: AD-MSCs = adipose-derived mesenchymal stem cells, BMAC = bone marrow aspirate concentrate, BM-MSCs = bone marrow mesenchymal stromal cells, Cl = confidence interval, HA = hyaluronic acid, HTO = high tibial osteotomy, IKDC = International Knee Documentation Committee, IL-1RA = IL-1 receptor antagonist, MSCs = mesenchymal stem cells, PBSC = peripheral blood stem cells, PRG = progenza, PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analysis, PRP
= platelet-poor plasma, RCTs = randomized controlled trials, SMD = standardized mean difference, VAS = Visual Analogue Scale, WOMAC = Western Ontario and McMaster Universities.

Keywords: knee osteoarthritis, meta-analysis, stem cell therapy

Umbilical cord-derived Wharton’s jelly for regenerative medicine applications

Download the PDF for the full article, the abstract is blow


Background: The last decade has seen an explosion in the interest in using biologics for regenerative medicine applications, including umbilical cord-derived Wharton’s Jelly. There is insufficient literature assessing the amount of growth factors, cytokines, hyaluronic acid, and extracellular vesicles including exosomes in these products. The present study reports the development of a novel Wharton’s jelly formulation and evaluates the presence of growth factors, cytokines, hyaluronic acid, and extracellular vesicles including exosomes.

Methods: Human umbilical cords were obtained from consenting caesarian section donors. The Wharton’s jelly was then isolated from the procured umbilical cord and formulated into an injectable form. Randomly selected samples from different batches were analyzed for sterility testing and to quantify the presence of growth factors, cytokines, hyaluronic acid, and extracellular vesicles.

Results: All samples passed the sterility test. Growth factors including IGFBP 1, 2, 3, 4, and 6, TGF-α, and PDGF-AA were detected. Several immunomodulatory cytokines, such as RANTES, IL-6R, and IL-16, were also detected. Proinflammatory cytokines MCSFR, MIP-1a; anti-inflammatory cytokines TNF-RI, TNF-RII, and IL-1RA; and homeostatic cytokines TIMP-1 and TIMP-2 were observed. Cytokines associated with wound healing, ICAM-1, G-CSF, GDF-15, and regenerative properties, GH, were also expressed. High concentrations of hyaluronic acid were observed. Particles in the extracellular vesicle size range were also detected and were enclosed by the membrane, indicative of true extracellular vesicles.

Conclusion: There are numerous growth factors, cytokines, hyaluronic acid, and extracellular vesicles present in the Wharton’s jelly formulation analyzed. The amount of these factors in Wharton’s jelly is higher compared with other biologics and may play a role in reducing inflammation and pain and augment healing of musculoskeletal injuries.

Keywords: Regenerative medicine, Musculoskeletal injuries, Osteoarthritis, Biologics, Umbilical cord, Wharton’s jelly, Growth factors, cytokines, Hyaluronic acid, Exosomes

Exosomes from acellular Wharton’s jelly of the human umbilical cord promote skin wound healing

Download the PDF for the full document. Below is the Abstract.


Background: Compromised wound healing has become a global public health challenge which presents a significant psychological, financial, and emotional burden on patients and physicians. We recently reported that acellular gelatinous Wharton’s jelly of the human umbilical cord enhances skin wound healing in vitro and in vivo in a murine model; however, the key player in the jelly which enhances wound healing is still unknown.

Methods: We performed mass spectrometry on acellular gelatinous Wharton’s jelly to elucidate the chemical structures of the molecules. Using an ultracentrifugation protocol, we isolated exosomes and treated fibroblasts with these exosomes to assess their proliferation and migration. Mice were subjected to a full-thickness skin biopsy experiment and treated with either control vehicle or vehicle containing exosomes. Isolated exosomes were subjected to further mass spectrometry analysis to determine their cargo.

Results: Subjecting the acellular gelatinous Wharton’s jelly to proteomics approaches, we detected a large amount of proteins that are characteristic of exosomes. Here, we show that the exosomes isolated from the acellular gelatinous Wharton’s jelly enhance cell viability and cell migration in vitro and enhance skin wound healing in the punch biopsy wound model in mice. Mass spectrometry analysis revealed that exosomes of Wharton’s jelly umbilical cord contain a large amount of alpha-2-macroglobulin, a protein which mimics the effect of acellular gelatinous Wharton’s jelly exosomes on wound healing.

Conclusions: Exosomes are being enriched in the native niche of the umbilical cord and can enhance wound healing in vivo through their cargo. Exosomes from the acellular gelatinous Wharton’s jelly and the cargo protein alpha-2- macroglobulin have tremendous potential as a noncellular, off-the-shelf therapeutic modality for wound healing.

Keywords: Skin, Umbilical cord, Wound healing, Wharton’s jelly, Exosomes, Stem cells

Acoustic Compression

Also known as Shockwave Therapy (ESWT)

The Non-Invasive Solution for an Active Lifestyle™

Acoustic Compression, also known as Extracorporeal Shockwave Therapy, is now available at Relief Medical Group!

Many patients have reported excellent results with only seven in-office sessions. Anesthesia is not required! ESWT is the healing technology that ends incurable foot, shoulder, elbow, and other areas of pain without surgery!

ESWT is also an effective, non-invasive treatment for Erectile Dysfunction and Cellulite Reduction!

The full price for consultation, examination, any necessary x-ray, and the seven weekly sessions of ESWT is only $1175 (when paid in advance—regularly $1275)

Only Seven Sessions Required! Please contact us for more information or any questions you may have!

Download information about Therapeutic Advances in Urology

ESWT has been used effectively worldwide to treat "insertional tendinopathies," such as:

  • Heel Pain (Plantar Fasciitis)
  • Tennis Elbow (Lateral Epicondylitis)
  • Shoulder Calcifications (Calcific Tendonitis)
  • Achilles Tendonitis
  • Knees (Patellar Tendonitis)
  • See our cosmetic pages to learn how this same technology is used to remove CELLULITE

Millions of people suffer from pain caused by inflammation of tendons and other soft tissues attached to bones, commonly referred to as "insertional tendinopathies” or enthesopathies".

How Does Extracorporeal Shockwave Treatment Work?

The widely accepted theory is that Extracorporeal Shockwave Treatment (ESWT) causes micro-trauma and controlled injury at the affected area, thereby leading to the formation of blood vessels (revascularization) which triggers the body's natural healing process and repair mechanisms. The sound waves are also thought to release adhesions and scarring to help increase mobility and optimize healing. Studies have shown a 60-80% success rate in significantly reducing or eliminating pain.

What Happens Before, During and After ESWT Treatment?

BEFORE: Patients will be instructed to discontinue medication containing aspirin or non-steroidal anti-inflammatory medications (e.g. Motrin) for several days before treatment (and most likely for up to 10 days following treatment) unless otherwise instructed by the treating doctor.

DURING: Treatment typically lasts 10 to 30 minutes and is performed in the office without the need for anesthetic. We use a high quality, low-medium energy ESWT unit.

AFTER: Patients may experience discomfort in the treated area after the effects of anesthesia have subsided. Some bruising, swelling, and temporary numbness is normal and expected. In the days immediately following treatment, many doctors will recommend stretching exercises to maintain mobility.

Patients can then typically resume normal activity. Heel pain patients are recommended to use custom orthotics when they have hyperpronation (flat feet) to optimize healing of the planter fascia and prevent recurrences.

Healing is generally near complete at about twelve weeks after the completion of the treatment visits, although patients may continue to experience additional reduction in pain and increased capacities thereafter.

What are Alternative Treatments?

Most doctors will first pursue conservative treatment options to reduce or eliminate pain. Conservative treatment may include such measures as rest, non-steroidal anti-inflammatory medications (NSAIDs), over-the-counter pain relievers, physical therapy, and orthotics (for heel pain). ESWT should be tried before cortisone injections, since injections increase the chances of tendon ruptures. Doctors will usually recommend ice, physiotherapy, exercises, and orthotics (heel lifts) prior to considering more aggressive approaches. However, when conservative treatments have failed, ESWT is increasingly being used to avoid traditional invasive surgery. Acoustic Compression is a more aggressive, more effective, and yet still conservative management for the conditions shown above.

Is This Treatment Right for Everyone?

You should speak to Dr. Cremata DC about your specific needs to see if Extracorporeal Shockwave Treatment is right for you. ESWT is not recommended for use on pregnant women, children, anyone with a pacemaker, or anyone on anti-coagulant therapy, or who has a history of bleeding problems.

How Do You Get Treatment?

Call Dr. Cremata, DC about your specific medical condition to see if Extracorporeal Shockwave Treatment (ESWT) is right for you.

The full price for consultation, examination, any necessary x-ray, and the weekly sessions of Acoustic Compression (Shockwave) is $995.00 (reg. $1195.00) when paid in advance. ONLY SEVEN VISITS REQUIRED!

Dr. Cremata, DC can provide additional complementary medical treatments as needed.

Pain Relief and Pain Management

Control of your pain is very important for your comfort, ability to sleep well, take care of yourself and your family, perform your job duties, etc.

At Relief Medical Group, we can provide you with prescription and non-prescription options to relieve your pain while you are undergoing treatment to improve the cause of your pain. We can dispense or prescribe various topical creams, anti-inflammatory agents, muscle relaxants, and other appropriate medications. When necessary for acute and severe pain, we can deliver these medications to you by injection for a rapid effect.

The ultimate goal is to improve your underlying condition enough so that you don’t need prescription medication for very long. The more conservative options of a topical medication cream, as opposed to oral medication, helps to prevent the dangerous and sometimes avoidable adverse effects from medications, such as stomach problems like ulcers, liver problems, or kidney toxicity.

A New Way of Thinking About Back Pain

Back pain

Back pain

The majority of back pain is preventable

This statement is at odds with the standard medical narrative for back pain. So much of western medicine focuses on treating injury and illness reactively- that is treating a problem symptomatically. But this relies on the logic that a problem need occur in the first place- why have we accepted this hook, line and sinker? A more logical way of treating pain is to prevent it in the first place. And while many types of back pain, the kinds that result from traumatic injury, genetic predisposition, or tumors, are unavoidable, the vast majority of back pain is preventable.

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Envisioning a New Year with Less Headaches

Headaches fremont

Headaches fremont

Chronic headache sufferers have little cause for cheer during the holidays

If you suffer from regular headaches, it can be hard to know when one will strike. This can be particularly prominent during the holiday season when you are surrounded by holiday cheer one minute, then stricken by a headache the next. Headaches menace people of all ages and health profiles, and our medical community is still at an early level of understanding the causes which contribute to this menace of society. If you suffer from headaches we are willing to wager that you are interested in prevention. At our office in Fremont, we realize that banishing headaches forever may not be realistic. However, we can strive to reduce the intensity, duration and frequency of your headaches to help you live a better life despite your condition

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Common Sense Saves You a lot of Back Pain

Chiropractor fremont

Chiropractor fremont

Listening to your body goes a long way

Too many people live their life at a pace too busy to consider their body’s internal signals. Technology is making it easier than ever to delegate the responsibility of listening to your body to your phone. There are apps that will ping reminding you to drink water, stretch, or take a break from the computer screeen. And while smart apps are designed to optimize our lives, we often find that all the optimization distracts us from what really matters: being in touch with our bodies. Besides, if you are too busy to remind yourself to stretch, you can just as easily ignore an app that tries to perform the same function. Now consider that instead of ignoring signals of muscle tension, you constantly ignore signals of pain. Human bodies are infinitely more powerful than we give them credit for: our capacity to perform everyday functions despite serious pain signals has the potential to cause a lot of problems in our lives. 

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