Joint Injuries

Knee injuries: Cartilage is a resilient and smooth elastic tissue, rubber-like padding that covers and protects the ends of long bones at the joints. Knee injury is often the result of deterioration to the cartilage due to overuse or wear and tear ^[36]. It occurs when tissue inhibitor of the metalloproteinase (TIMP)-2 level decreases thereby allowing matrix metalloproteinases (MMPs) 2 and 13 to become overactive and cause different degrees of cartilage degradation ^[37]. 

Tendon or ligament damage: A tendon is an elasticated tough tissue that attaches muscle to the bone while a ligament attaches bone to bone. Overuse and frequently repeated movements can lead to eventual tendon and ligament damage, particularly in the elbow, Achilles, bicep and hamstring tendons ^[36]. It is caused by altered mechanical phenomena such as laxity ^{[38,39,40,41]}, decreased stiffness ^[41,42,43] and altered viscoelastic responses ^[42] coupled with the onset of collagen disorganization ^[43,44], fibroblast necrosis ^[41] and nociceptor activation ^[45].

Stress fractures: This type of injury occurs when a substantial amount of strain is placed on the body’s bones and joints. A common example in sport is shin splints and nearly all sports carry the risk of stress fracture ^[36]. The most common bone injured was the tibia (49.1 %), followed by the tarsals (25.3%), metatarsals (8.8%), femur (7.2%), fibula (6.6%), pelvis (1.6%), sesamoids (0.9%) and spine (0.6%). Stress fractures were bilateral in 16.6% of cases ^[46].

Back injuries: Lower back pain is a debilitating problem faced by athletes ^[36]. Injury rates were significantly higher in American football and gymnastics. Of the 4,790 athletes examined, 80% of injuries occurred during practice, 6% during competitions, and 14% during preseason conditioning. Muscle strains occurred with much greater frequency than other types of injuries, and acute back injuries were much more prevalent (59%) than overuse injuries (12%) or injuries associated with pre-existing conditions (29%) ^[47].

With the extreme pressure and demands of sports, professional athletes have become some of the earliest adopters of MSC therapy. Most of the athletes mentioned below opted to have their own bone marrow or adipose MSCs harvested then injected into damaged areas, such as:

How Our Products Can Treat Joint Injuries

We use products derived from human baby umbilical cord tissues - Wharton's Jelly MSCs (wjMSCs) - in all our therapy programs. wjMSCs are special because they can:

• transform into chondrocytes (which form cartilage) ^{[83,84,85,86,87,88,89,90]}.
• transform into osteocytes (which form bone) ^{[83,84,86,87,88,89,90,91,92,93]}.
• transform into myocytes (which form skeletal muscles) ^{[83,84,86,87,88,89]}.
• improve muscle regeneration ^[94,95].
• improve strength and volume of injured skeletal muscle ^[96].
• restore the structure and strength of tendons and ligaments ^[97,98].
• reduce inflammation ^{[99,100,101,102,103,104,105,106,107,108]}.
• prevent rejection by regulating the immune system (immunomodulation) ^{[99,104,106,107,109,110,111,112,113,114]}.
• incapable of forming tumours ^{[109,111,114,115,116]}.

Treating Joint Injuries

There are currently numerous clinical trials exploring the use of wjMSCs in the treatment of joint injuries. These have been registered but results and findings have yet to be posted ^{[117,118,119,120,121,122,123,124,125,126]}.

Cartilage Degeneration:

Osteoarthritis is a chronic degenerative disorder that ultimately leads to a gradual deterioration of joint cartilage. Its onset can be caused by a combination of genes, age, weight gain, injury and overuse as well as bone, joint or metabolic disorders. Repeated damage to joints, tendons and ligaments in combination with any of the above factors speeds up cartilage breakdown.

A 2008 American study found that 24 weeks post-treatment with the patient’s own (autologous) bone marrow MSCs (bmMSCs), the patient; who had MRI-proven degenerative joint disease in both knees; experienced statistically significant cartilage and meniscus growth on MRI, as well as increased range of motion and decreased modified visual analog scale (VAS) pain scores ^[127]. 

In 2015, researchers at Royan Institute for Stem Cell Biology and Technology, Iran, treated 18 patients with different joint involvements (osteoarthritis in the knee, ankle or hip) with autologous bmMSCs. By the end of 30 months, all patients exhibited therapeutic benefits such as increased walking distance, decreased visual analog scale (VAS), and total Western Ontario and McMaster Universities OA Index (WOMAC) scores which were confirmed by MRI ^[128].

A 2016 Indian clinical trial treated 60 knee osteoarthritis patients with donor (allogeneic) bmMSCs. They were divided into 5 groups of 12 people each and each knee was injected with (1) a placebo or (2) 25 million bmMSCs, 50 million bmMSCs, 75 million bmMSCs, or 150 million bmMSCs. The study found that patients who received 25 million allogeneic bmMSCs per knee showed a trend towards improvement as well as effective pain reduction ^[129].

Later in 2018, Chilean researchers treated 26 knee osteoarthritis patients with allogeneic Wharton’s Jelly MSCs. They were divided as follows: (1) 8 patients received 2 doses of hyaluronic acid 6 months apart, (2) 9 patients with 1 dose of 20 million wjMSCs and (3) 9 patients with 2 doses of 20 million wjMSCs 6 months apart (a total of 40 million wjMSCs per patient). At the end of the trial, only the 18 MSC‐treated patients showed significant improvements in pain and function with an 86% reduction in pain and an 89% reduction in disability and improvements lasting the entire duration of the evaluation period. The wjMSC-3 group exhibited a significant advantage in pain reduction with their pain scores reaching significantly lower levels compared to the other 2 groups at the 12-month follow‐up ^[130].

Tendon or Ligament Damage:

In 2013, researchers from the National Yang-Ming University, Taiwan evaluated the efficacy of rat bmMSCs that had been cultured under 2 different conditions; low oxygen (hypoxic) and normal (normoxic); in treating an injured Achilles tendon. 50 Sprague-Dawley rats were used for the experiments, with 2 rats as the source of bmMSCs. The cut Achilles tendons in the rats were equally divided into 3 groups: hypoxic bmMSC, normoxic bmMSC, and non-treated (vehicle control). Biomechanical testing, histologic analysis, and immunohistochemical evaluation showed hypoxic bmMSCs had increased healing capacity compared with normoxic bmMSCs. This was shown by a greater ultimate failure load in hypoxic bmMSC group at 2- and 4-weeks post-transplantation. This was subsequently confirmed with histologic analysis and immunohistochemical evaluation. 5-bromo-2-deoxyuridine labeling of MSCs before injection confirmed the incorporation and retention of transplanted cells at the rupture site ^[131].

Meniscus:

In 2013, Japanese researchers conducted a large animal study in 10 skeletally mature pigs who underwent resection of the anterior half of the medial meniscus of both knees. 2 weeks later, 7 pigs received intra-articular injections of 50 million synovial MSCs in 1 only knee at 0, 2, and 4 weeks and were evaluated via MRI at 2, 4, 8, 12, and 16 weeks. 3 pigs were left untreated. Macroscopic and histologic evaluation was also performed on the regenerated menisci at 16 weeks. It was shown that meniscal regeneration was significantly better in the 7 sMSC-treated knees versus the 13 untreated knees. Histologic and MRI evaluation showed increased staining with Safranin O, larger sections of type I and type II collagen, and significantly lower T2 signal intensity in the sMSC-treated knees from 2 weeks through 16 weeks. Articular cartilage on the medial femoral condyle was found to be significantly better preserved macroscopically in the sMSC-treated knees of all 7 recipients based on the International Cartilage Repair Society score for macroscopic observation and MRI. Articular cartilage in the sMSC-treated knees was found to be better preserved at all time points and had significantly better MRI scores from 8 weeks onward ^[132].

An American randomized double-blind controlled trial of 55 patients who underwent partial meniscectomy surgery. 7 to 10 days after the surgery, 36 patients received an injection of allogeneic bmMSCs into the superolateral aspect of the suprapatellar pouch; 18 patients in Group A received 50 million bmMSCs, 18 patients in Group B received 150 million bmMSCs and 19 patients in the control group did not receive bmMSCs. After 12 months of follow-up, the study concluded that allogeneic bmMSCs have the potential to improve the overall condition of the knee joint, increase meniscal volume by 15%; as evidenced by MRI scans as well as a reduction in pain ^[133].

Back Injuries:

The first human trial using autologous bmMSCs was conducted in 2011 by Centro Médico Teknon, Spain. They explored the efficacy of bMSCs in treating lumbar disc degeneration. In as little as 3 months, all participants reported an 85% decrease in pain and disability. While the trial noted that disc height did not increase, it found that water content in the nucleus pulposus had significantly increased in a year ^[134]. 

In 2014, the General Hospital of Armed Police Force in China transplanted allogeneic wjMSCs into 2 patients with chronic discogenic lower back pain. Both patients reported an immediate improvement in pain and functionality. Their Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) remained decreased 2 years post-therapy ^[135].

A 2014 Phase 2 clinical trial in Melbourne, Australia treated 100 patients afflicted with disc degeneration that caused chronic lower back pain with a single intra-discal injection of 6 million allogeneic precursor cells (MPCs). The treatment resulted in meaningful improvements in both pain and function that were durable for at least 3 years. MRI scans also found that the damaged discs appeared to have been rebuilt. At the time of writing, a Phase 3 clinical program has completed enrollment of 404 patients and is currently underway ^[136].

A 2015 multicenter study injected autologous bmMSCs directly into degenerated discs of 26 patients. At the end of 12 months, their average Oswestry Disability Index (ODI) reduced from 56.5 to 25.0 while the average VAS score reduced from 79.3 to 33.2 ^[137].

Later that year, the CHA University in South Korea found that treatment using human wjMSCs in rabbit models of intervertebral disc degeneration significantly restored disc water content after just 12 weeks. Researchers transplanted wjMSCs directly into the affected disc and found that repair and restoration were exacted via cell signaling (paracrine) mechanisms ^[138]. 

Cyrona’s Program

Achieving high standards in our work is of paramount importance to us. Depending on a patient’s needs, we combine our premium grade Passage 2 wjMSCs with physiotherapy, occupational therapy, speech and language therapy and/or rehabilitative medicine. 

Learn more about our Products and Programs.

Why Choose Cyrona?

• Latest cellular research and technology.
• Unique, tailored therapy outlines.
• Products that meet international standards.
• Microbiology & clinical team with extensive experience in advanced medicine.
• Board-certified physicians geared toward patient safety.
• Fact-based information from clinical studies and trials.
• No outlandish promises of a one-stop-cure or false improvement rates.

Therapy Packages

All our therapy packages come inclusive of:

INTERNATIONAL PATIENTS

• Premium grade Passage 2 wjMSCs.
• Treatment by qualified specialist(s).
• Certificate of Analysis (CoA).
• Airport transfer.
• Transportation to & from therapy session(s).
• Accommodation.
• Hospital room for therapy.

LOCAL PATIENTS

• Premium grade Passage 2 wjMSCs.
• Treatment by qualified specialist(s).
• Certificate of Analysis (CoA).
• Transportation to & from therapy session(s).
• Hospital room for therapy.

How Do We Proceed

All our therapies are charged based on the number of wjMSCs and supplementary infusions required for the patient’s specific condition. As no two people are alike, our specialists review each patient’s medical reports before tailoring a therapy catered to addressing his or her individual needs.

You may chat with one of our Customer Care Representatives or send an e-mail detailing the patient’s condition to one of our Liaison Officers. It would expedite the process if you can provide us with:

• Imaging results (MRI scan / CT scan / X-Ray).
• Haematology reports (blood test).
• Doctor’s assessment reports.
• Pictures or videos of the patient (if relevant).

Upon getting in touch with us, a Liaison Officer evaluates and assigns the case to the specialist best equipped to treat the condition. A therapy, unique only to the patient, is drawn up and a price quoted accordingly.

Should you decide to proceed with therapy, our specialists require that all patients have Cancer Marker Screening performed in their country of residence before travelling to us for therapy. If the patient has had Cancer Marker Screening within the last 3 months, you may e-mail those results to us. In the event that the patient’s Cancer Marker Screening results are not satisfactory, our specialists will refuse to proceed with therapy. It is for this reason that we request that patients have Cancer Marker Screening performed in their country of residence prior to travelling to us.

One week prior to arrival, a deposit payment is required in order to arrange accommodation and transportation.

Full payment is required to be made one-day prior to therapy commencement.

Post-treatment, our specialist will provide the patient with a post-treatment protocol as well as what to expect on his or her journey towards a better, and hopefully, healthier new life.

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