Regenerative therapies are a spectrum of cutting edge therapeutic techniques used to naturally treat and heal the cause of a painful condition rather than masking the symptom. Regenerative therapies stimulate and accelerate your own body’s natural ability to heal itself. Two of the most effective Regenerative therapies include platelet-rich plasma and stem cell injections.
Platelet Rich Plasma or PRP is a volume of plasma of autologous blood having a platelet concentration above the baseline (baseline for platelets in a human are 150,000 – 350,000 platelets per microliter). Platelets facilitate healing by stimulating the release of different growth factors. The growth factors recruit stem cells that facilitate healing, repair, or regeneration of the injured tissue. PRP is injected directly into injured tissue stimulating a healing response in a more powerful form.
The main components of blood are Red Blood Cells (carry oxygen from the lungs and deliver it to the body tissues), White Blood Cells (form our immune system and help the body to fight infection and foreign materials), Platelets and Plasma.
Platelets normally circulate within the blood stream and are responsible for blood clotting and initiating a healing response in an acute injury. Platelets have several functions, they help control bleeding (hemostasis), they help in the building of new tissue (act as scaffold for tissue regeneration called Extra Cellular Matrix or ECM), stem cell attraction and binding, without platelets undifferentiated stem cells would not know what to transform into until growth factors are released from the platelets, finally platelets divide, multiply and differentiate to become the healing cells for injured tissue. Platelets are activated by Thrombin and other factors which cause a change in their structure and the release of multiple growth factors. These growth factors bind themselves to the receptors of the cell causing intracellular changes down to the nucleus and affecting its DNA. The result is a change in the performance and function of the cell.
PRP can be used in Surgical Procedures, Orthopaedics, Spine, MSK, Pain Management, Urology, Maxillofacial, Cardio, Aesthetics and other specialties. Platelets are the natural healing element for any damaged tissue. Delivery of the PRP can be injected or sprayed on the injured or damaged area.
Ultrasound or fluoroscopy is recommended to be used in MSK or any injection of PRP where the injured area can't be visualised. Studies have shown that using ultrasound or fluoroscopy will increase the accuracy of delivering the PRP to the injured tissue.
Hip and knee osteoarthritis (mild to moderate)
Osteochondritis dissecans (OCD)
Bone non-union, pseudoarthrosis
Spinal fusion (to accelarate regeneration and bone healing)
Avascular necrosis (osteonecrosis)
Meniscus injury
Labrum tear
Back pain
Disc problems (DDD, herniated disc)
ACL reconstruction
Jumper's knee (patellar tendonitis)
Tennis elbow (lateral epicondylitis)
Gluteal tendinopathy
Biceps tendinitis & tendinosis
Rotator cuff tear & tendinopathy
Plantar fasciitis
Carpal tunnel syndrome
Nerve root pain
Neuropathic pain
Trigeminal neuralgia
Source: Dr. Sabino Padilla, TOBI presentation, 2021
Pain from the injections
Skin redness, haematoma
Muscle pain
Joint pain
Pain in the treated area lasting one to two weeks
Infection
How patients respond to treatment varies; in most cases 1-3, in some cases up to 6 treatments are necessary. 4-6 weeks should elapse between two treatments. There is no limit to the maximum number of treatments, and the probability of side effects does not increase with the number of injections.
PRP treatment helps to rebuild the tendons and ligaments, but it is not an immediate help. The intervention stimulates the growth and regeneration of ligaments and tendons, which requires time and rehabilitation. After the treatment, patients may feel mild to moderate pain at the injection site. In the two weeks following the intervention, it is recommended to only gradually load the limb, overexertion must be avoided. Starting physiotherapy as soon as possible is important and will further enhance the effectiveness of the PRP therapy.
According to research, steroid injections can weaken tissues in the long term. Steroid injections can temporarily reduce pain and reduce inflammation, but they do not aid in healing. Platelet-rich blood plasma treatment heals and strengthens tendons and ligaments, making them up to 40% stronger and thicker in some cases.
The majority of protocols (80%) reviewed did not limit preinjection NSAID use; however, 56% of protocols studied restricted NSAID use post-PRP injection, most commonly for at least 2 weeks. NSAIDs can impair platelet function by inhibiting the function of both COX-1 and COX-2 path- ways, which forms the rationale for limiting NSAID use prior to PRP preparation. A number of investigations have demonstrated decreased platelet activation and aggrega- tion following NSAID use both in animal models and humans.This inhibitory effect appears to be decreased with the use of COX-2 selective NSAIDs. The daily use of aspirin prior to PRP preparation also affects the resultant PRP, and leads to a reduction in vascular endothelial growth factor, platelet-derived growth factor-AB, and transforming growth factor-β1.Arguments exist to limit NSAIDs following PRP adminis- tration as well. In a murine model of Achilles ten- dinopathy, administration of ibuprofen during the inflammatory stage of healing interfered with extracellu- lar matrix remodeling and ultimately led to decreased tensile strength in the healed tendon. Similar results, including abnormal fiber organization and decreased ten- sile strength, were seen in a rat model of tendinopathy where ibuprofen was delivered in the first week after injury. However, when delivered after 1 week following injury, no detrimental effects were seen, suggesting that NSAIDs interfere in tendon healing in a time dependent manner, most pronounced in the early, inflammatory phase of healing. The effects of NSAIDs in human tendinopathy are less clear. In chronic Achilles tendinosis, ibuprofen did not affect the expression of collagen by fibroblasts but did decrease DNA synthesis during the proliferative phase of healing. The effect of NSAIDs on human tendon tissue, when given during the inflammatory phase following injury, remains unknown. Taken together, these results from both animal and human studies form a reasonable rationale to limit NSAIDs both prior to PRP preparation and during the early period following PRP administration.
Source: Townsend, 2020
Absolute Contraindications:
Platelet dysfunction syndrome
Critical thrombocytopenia
Hemodynamic instability
Septicemia
Local infection at the site of the procedure
Relative Contraindications:
Consistent use of NSAIDs within 48 hours of procedure
Corticosteroid injection at treatment site within 1 month
Systemic use of coriticosteroids within 2 weeks
Regular smoking
Recent fever or illness
Cancer- especially hematopoetic or of bone
Chronic Liver Pathology
Hypofibrinogenaemia
HGB < 100 g/L
Platelet count < 105 10*9/L
Give your patient the best and only use a validated regenerative system. The stem cell and PRP protocol developed by APEX Biologix is approved by the US Food and Drug Administration (FDA). With the recommended preparation protocol, 6 to 9 times platelet concentration is achievable and the clinical quality of the product is guaranteed.
A certain number of platelet and growth factor concentration is needed for clinical efficacy. According to the Nature publication in 2021, ‘an absolute count of 10 billion platelets is crucial in a PRP formulation to have long sustained chondroprotective effect up to one year in moderate knee OA’. This quantity can only be made from larger amounts of blood. More blood means more platelets in the PRP. From 60 mL blood, 6 to 8 mL PRP can be produced having the necessary concentration.
Stems cells are "undifferentiated" cells, which allow them to develop into another type of cell that is required to repair or replace damaged tissue.
Stem cell therapy can repair tissues that are too damaged to heal on their own. Stem cells can stimulate the formation of cartilage, tendon, ligaments, bone and fibrous connective tissues. Stem cells are obtained from the patient's own tissue. During the intervention, the stem cell concentrate is injected into the damaged areas of the body, where they promote regeneration and healing. These therapies are a safe, non-surgical treatment option for most chronic pain, wound management and aesthetic disorders.
Electron micrograph of stem cells (colour corrected for visibility)
Source: fda.gov
Mesenchymal stem cells (MSCs) are undifferentiated cells capable of self-renewal and differentiating into other types of cells. Stem cells can stimulate the recovery of damaged tissue, the formation of cartilage, tendons, ligaments, bones and fibrous connective tissue.
At the site of hematopoiesis in adulthood, in the bone marrow, we find the heterogeneously composed bone marrow stroma (which, in addition to hematopoietic cells, provides the microenvironment essential for their functioning). Multipotent stem cells, from which all the cell types of the stroma (the structural or connective part of a tissue or organ) can develop, are called mesenchymal stem cells or stromal stem cells. Cell types of the stroma can be:
chronodcytes - cartilage generation (chondrocytes, cartilage generation),
osteoblasts - bone formation (osteoblasts, bone formation),
adipocytes - fat tissue (adipocytes, adipose),
myocytes - muscle tissue (myocytes, muscle),
endothelial cells - vascular system, circulation (endothelial cells), and
fibroblasts - connective tissue (fibroblasts).
MSCs can have both anti-inflammatory and pro-inflammatory effects, enabling the treatment of a wide range of immune system disorders and inflammatory diseases.
Bone marrow-derived MSCs (BM-MSCs) are considered the best cell source and serve as a standard for comparing MSCs from other sources (e.g. adipose tissue) [Ullah I. et al., Human mesenchymal stem cells - current trends and future prospective, Bioscience Reports, 2015].
From a therapeutic point of view, the most promising of tissue stem cells seems to be the MSCs: these cells can be easily isolated and cultured - in addition to bone marrow, they can also be obtained from many other easily accessible tissues of mesenchymal origin, such as adipose tissue - and appear surprisingly plastic in in vitro and in vivo experiments .
The clinical application of MSCs can be basically attributed to their four key biological properties:
after tissue damage, they can enter the inflammatory sites (during the injection),
they can differentiate into several cell types, including cartilage, muscle, bone, connective tissue and fat cells,
various bioactive molecules are secreted, thereby stimulating the regeneration of damaged cells,
they suppress inflammation and have immunomodulating ability.
Because of the characteristics of bone marrow-derived MSCs, they play an important role in regenerative medicine. Its main features are:
easy isolation from bone marrow without immunological problems, possibility of in vitro breeding within a short period of time,
its biological durability with minimal loss of effect at the point-of-care,
no serious side effects can be detected during autologous or allogeneic therapies.
A special technique for maximizing stem cell concentration established by Dr. Philippe Hernigou. The procedure is performed by Dr. Richard Rosenthal.
For more information call: +36 30 913 2676