Treatment Of Degenerative Disease Research Articles

Mechanisms of Action of Human Mesenchymal Stem Cells in Tissue Repair Regeneration and their Implications

Cell replacement therapy holds a promising future in the treatment of degenerative diseases related to neuronal, cardiac and bone tissues. In such kind of diseases, there is a progressive loss of specific types of cells. Currently the most upcoming and trusted cell candidate is Mesenchymal Stem Cells (MSCs) as these cells are easy to isolate from the tissue, easy to maintain and expand and no ethical concerns are linked. MSCs can be obtained from a number of sources like bone marrow, umbilical cord blood, umbilical cord, dental pulp, adipose tissues, etc. MSCs help in tissue repair and regeneration by various mechanisms of action like cell differentiation, immunomodulation, paracrine effect, etc. The future of regenerative medicine lies in tissue engineering and exploiting various properties to yield maximum output. In the current review article, we have targeted the repair and regeneration mechanisms of MSCs in neurodegenerative diseases, cardiac diseases and those related to bones. Yet there is a lot to understand, discover and then understand again about the molecular mechanisms of MSCs and then applying this knowledge in developing the therapy to get maximum repair and regeneration of concerned tissue and in turn the recovery of the patient.

Laser Shock-Wave Destruction of the Mucous Membrane and Skin Tissues as a Method of Treatment of Pathological Processes in Gynecology

The article substantiates a new method of treatment of degenerative diseases in gynecology by controlled destruction with laser shock waves poorly absorbed by biological tissues. The shock-wave process is initiated using finely dispersed absorbing particles deposited on the surface of pathological tissues. Absorption of laser radiation by the particles leads to their explosion accompanied by generation of elastic waves. Propagation of these waves in the surface layer of the surrounding biological tissue leads to its destruction. Such destruction can provide a precision therapeutic effect with controlled depth and area.

Single-Cell Analysis of SMN Reveals Its Broader Role in Neuromuscular Disease

The mechanism underlying selective motor neuron (MN) death remains an essential question in the MN disease field. The MN disease spinal muscular atrophy (SMA) is attributable to reduced levels of the ubiquitous protein SMN. Here, we report that SMN levels are widely variable in MNs within a single genetic background and that this heterogeneity is seen not only in SMA MNs but also in MNs derived from controls and amyotrophic lateral sclerosis (ALS) patients. Furthermore, cells with low SMN are more susceptible to cell death. These findings raise the important clinical implication that some SMN-elevating therapeutics might be effective in MN diseases besides SMA. Supporting this, we found that increasing SMN across all MN populations using an Nedd8-activating enzyme inhibitor promotes survival in both SMA and ALS-derived MNs. Altogether, our work demonstrates that examination of human neurons at the single-cell level can reveal alternative strategies to be explored in the treatment of degenerative diseases.

Comparison Between Acrylic Cage and Polyetheretherketone (PEEK) Cage in Single-level Anterior Cervical Discectomy and Fusion: A Randomized Clinical Trial.

Prospective, single-blind randomized-controlled clinical study. To compare polyetheretherketone (PEEK) cage with a novel Acrylic cage to find out which fusion cage yielded better clinical outcomes following single-level anterior cervical discectomy and fusion (ACDF). ACDF is considered a standard neurosurgical treatment for degenerative diseases of cervical intervertebral disks. There are many options, including bone grafts, bone cement, and spacers made of titanium, carbon fiber, and synthetic materials, used to restore physiological disk height and enhance spinal fusion, but the ideal device, which would provide immediate structural support and subsequent osteointegration and stability, has not been identified yet. To overcome this, we designed a new, inexpensive Acrylic cage. A total of 64 patients were eligible to participate and were randomly allocated to undergo ACDF either with Acrylic interbody fusion cage filled with bone substitute (n=32) or PEEK cage (n=32). Nurick's grading was used for quantifying the neurological deficit. Clinical and radiologic outcome was assessed preoperatively, immediately after surgery, and subsequently at 2, 6, and 12 months of follow-up using Odom's criteria and dynamic radiographs (flexion-extension) and computed tomography scans, respectively. There was a statistically significant improvement in the clinical outcomes of the Acrylic cage group compared with the PEEK cage group (mean difference: -0.438; 95% confidence interval, -0.807 to -0.068; P=0.016). There was a statistically significant difference in disk space height increase between the 2 groups at the 6- and 12-month follow-up. The Acrylic cage achieved higher fusion rate (good fusion) than the PEEK cage (96.9% vs. 93.8%). Intervertebral angle demonstrated a significant difference among the 2 treated groups throughout the follow-up period. This study suggests that the use of Acrylic cage is associated with good clinical and radiologic outcomes and it can be therefore a good substitute for bone graft and other cages in ACDF.

Clinical value of one-level oblique lateral interbody fusion in the treatment of degenerative lumbar disc diseases

Objective To evaluate the clinical outcomes of one-level oblique lateral interbody fusion (OLIF) for the treatment of degenerative lumbar diseases. Methods A total of 36 patients, 11 males and 25 females with ages from 32 to 75 (average 55.2 ± 13.6 years), underwent one-level OLIF with or without posterior pedicle screw-rod instrumentations from October 2014 to May 2016. The index diagnosis was discogenic back pain in 15 cases, and spondylolisthesis with or without segmental instability in 21 cases. The distribution of operative level was 30 cases at L4/5 and 6 cases at L3/4. The changes of serum level of creatinine kinase was measured 1 and 3 days post-operatively, and compared to that of the pre-operative one. Clinical outcomes were evaluated using visual analogue scale (VAS) and Oswestry disability questionnaire (ODI) scores. Lumbar X-ray was taken and the clinical outcomes were re-assessed. Results 25 in the 36 patients underwent supplementary posterior pedicle screw-rod instrumentation with OLIF procedures. The operation lasted for 46-175 min, with a mean duration of (112±43) min. Blood loss during the operation was 30-180 ml, with a mean of (63 ± 35) ml. Average length of stay was (4.5±2.1) d, ranging from 3-7 d. Serum level of creatinine kinase was (63.5±16.8) IU/L before operation, (416.8±152.1) IU/L 1 day after operation, (112.4±37.5) IU/L 3 days after operation. The VAS and ODI score decreased from (8.3±2.3) pre-operatively to (1.6±0.4) 6 months post-operatively, and from (69.2±17.5) to (10.7±2.7), respectively. The total incidence of complications was 25%, including 8.3% of intra-operative complications (3 cases of cage subsidence) and 16.7% of post-operative ones. The latter consisted of ipsilateral hip flexor weakness in 1, ipsilateral anterior thigh pain in 1, contralateral pain in flexion of hip in 1, ipsilateral sympathetic chain injury in 1, and pain in area of iliac bone donor site in 2. All symptoms were released or disappeared during follow-up. Conclusion OLIF as a novel technique for spinal surgical management showed excellent short-term outcomes. Clinical results with long-term follow-up are required. Key words: Lumbar vertebrae; Spinal fusion; Clinical protocols

Healthy properties of green and white teas: an update.

Green tea has been consumed for centuries in Japan, China and Morocco. White tea, which is considered a variety of green tea, is mostly consumed in China and is very appreciated for its flavor. Currently the consumption of both types of tea has been extended to the western countries even as a functional ingredient. A group of polyphenols called catechins stands out among their bioactive components, the most abundant being the (-) epigallocatechin gallate, with high antioxidant power. Teas also contain other phenolic compounds such as gallic, caffeic, chlorogenic or cinnamic acids, quercetin and proanthocyanidols, caffeine, theophylline, l-theanine and minerals such as fluorine, manganese or chromium. Investigations have mainly been focused on their antioxidant potential and their implication in the prevention and treatment of degenerative diseases. Several studies have evaluated their role in cardiovascular diseases, body weight control, bone mass increase, protection against neurodegenerative diseases and improvement of type 2 diabetes, among other pathologies. The main points of controversy are the design and interpretation of epidemiological and human intervention studies and the lack of information on catechins availability, metabolism and biotransformation. This review compiles and analyzes the latest peer-reviewed papers published from 2002 up to February 2017, including systematic reviews and meta-analyses.

Reflections about Osteoarthritis and Curcuma longa.

Osteoarthritis (OA) is a chronic inflammatory degenerative process that affects joints such as the hands, hips, shoulders, feet, spine, and especially knees in millions of people worldwide. Some authors have shown that Curcuma longa components may exhibit benefic effects in the treatment of degenerative diseases as OA. This plant belongs to the family Zingiberaceae and it is popularly known as turmeric or saffron. This review intended to perform a retrospective search to identify studies involving humans and animal models. This review was based on articles linking OA and C. longa. Databases as Medline, Science Direct, and Lilacs were consulted and a retrospective search was carried out in order to identify studies involving humans and animal models. The curcuminoids from C. longa exhibit actions at different locations in the pathogenesis of OA once it may play an important role as anti-inflammatory, down-regulating enzymes as phospholipase A2, cyclooxygenase-2, and lipoxygenases, and reducing tumor necrosis factor-alpha-and interleukins such as interleukin-1β (IL-1β), IL-6, and IL-8. They also act as inducer of apoptosis in synoviocytes, decreasing the inflammation process and may also reduce the synthesis of reactive oxygen species. For these reasons, new pharmaceutical technology and pharmacological studies should be proposed to determine the dose, the best delivery vehicle, pharmaceutical formulation and route of administration of this plant so its use as an adjunct in the treatment of OA may become a reality in clinical practice.

Physical Therapy in Elderly Suffering from Degenerative Diseases.

Introduction:Osteoarthritis of the joints (osteoarthritis or arthritis) represents the largest group of rheumatic diseases. Within rheumatic diseases 50% are degenerative rheumatic diseases, 10% inflammatory and 40% extra-articular.Goal:To determine the modalities of physical therapy for elderly with degenerative diseases.Material and methods:The study is retrospective-prospective and descriptive. The survey conducted included 25 patients with degenerative diseases of the musculoskeletal and nervous systems in Gerontology Center in Sarajevo, from May 1, 2014- April 30, 2015. As research instruments were used: Questionnaire for users of physical therapy in Gerontology Center in Sarajevo, self-developed, visual-analog scale to assess pain and patient records.Results:Of the total number of patients with degenerative diseases (25), 10 (40%) were male and 15 (60%) were female. The most common degenerative disease is knee osteoarthritis which had 11 patients (29%), 3 males and 8 females. From physical therapy modalities in the treatment of degenerative diseases at the Gerontology Center in Sarajevo, kinetic therapy was administered to all patients, followed by manual massage and TENS in 15 cases (60%). From twenty-two patients, who completed a questionnaire, 11 (50%, 2 male and 9 female) rated their health as poor. Seven patients (32%, 3 male and 4 female) assessed their health as good. Three patients (14%, 2 male and 1 female) rated their health as very poor, and one patient (4%, 1 male) rated its health as very good.Conclusion:The Research Physical therapy in elderly with degenerative diseases is a pilot project, which highlights the need for: Conducting research for a longer time period, with a larger sample; Quality of keeping health records; Implementation of a continuous evaluation of functional status and; Stricter control for optimal effectiveness of physical therapy in order to improve the quality of life of elderly patients.

Evaluation of outcomes of surgical treatment for degenerative diseases of the spine

The paper presents a review of the current literature devoted to estimation of outcomes of surgical treatment for degenerative changes in the spine using scales, tests and questionnaires. The literature search in domestic and foreign bibliographic databases has been carried out, and the use of scales, tests and questionnaires in spinal surgery was analyzed. The review presents requirements for scales, tests and questionnaires, examines the evaluation of clinical and patient-reported outcomes, and describes the advantages of multifactorial outcome evaluation. The multifactorial evaluation of outcomes is illustrated by the example of degenerative changes in the cervical spine, and includes a clinical case of surgical treatment for cervical myelopathy. The limitations of scales, tests and questionnaires are also discussed.

Percutaneous endoscopic discectomy in the treatment of patients with degenerative diseases of the lumbosacral spine

to evaluate the efficacy of percutaneous endoscopic discectomy in the treatment of herniated lumbar discs in patients with radicular pain syndrome. We conducted a cohort retrospective study that included 69 patients who underwent herniated disc removal using the percutaneous endoscopic technique. Surgery was performed through two approaches: the intralaminar approach was used in 44 patients, and the transforaminal approach was used in 25 patients. To assess the efficacy of surgery, we used a visual analogue scale (VAS) of pain: the intensity of local pain (VAS1) and the intensity of radicular pain (VAS2). Changes in the quality of life and ability to work were assessed by using the Oswestry scale; patient satisfaction with treatment was assessed by using the MacNab scale. The mean follow-up period after surgery was 24 months. An analysis of changes in the pain syndrome (VAS1 and VAS2) before surgery and in the early postoperative period demonstrated a significant regression of pain regardless of the approach type (r=0.25). Patients' survey (MacNab scale) in the long-term postoperative period revealed no unsatisfactory results; excellent, good, and satisfactory results were observed in 21 (30%), 32 (46%), and 16 (24%) patients, respectively. Percutaneous endoscopic discectomy is an effective surgical treatment for degenerative diseases of the lumbosacral spine, providing excellent and good treatment outcomes in most operated patients.

The Effects of BMP-2, miR-31, miR-106a, and miR-148a on Osteogenic Differentiation of MSCs Derived from Amnion in Comparison with MSCs Derived from the Bone Marrow.

Mesenchymal stromal cells (MSCs) offering valuable anticipations for the treatment of degenerative diseases. They can be found in many tissues including amnion. MSCs from amnion (AM-MSCs) can differentiate into osteoblast similar to that of bone marrow-derived MSCs (BM-MSCs). However, the ability is not much efficient compared to BM-MSCs. This study aimed to examine the effects of BMP-2 and miRNAs on osteogenic differentiation of AM-MSCs compared to those of BM-MSCs. The osteogenic differentiation capacity after miRNA treatment was assessed by ALP expression, ALP activity, and osteogenic marker gene expression. The results showed that the osteogenic differentiation capacity increased after BMP-2 treatment both in AM-MSCs and BM-MSCs. MiR-31, miR-106a, and miR-148a were downregulated during the osteogenic differentiation. After transfection with anti-miRNAs, ALP activity and osteogenic genes were increased over the time of differentiation. The data lead to the potential for using AM-MSCs as an alternative source for bone regeneration. Moreover, the information of miRNA expression and function during osteogenic differentiation may be useful for the development of new therapeutics or enhanced an in vitro culture technique required for stem cell-based therapies in the bone regeneration.

Design of a slideable pedicle screw-rod system and its efficacy in the treatment of lumbar spine fusion

Objective To investigate the efficacy and safety of a novel slideable pedicle screw-rod system in the treatment of lumbar degenerative diseases. Methods Analysed 71 patients (47 males and 24 females) with lumbar degenerative diseases underwent lumbar fusion using the novel slideable pedicle screw-rod system from June 2014 to June 2016, aged 30-73 years by average 57.6 years. All patients were divided into 2 groups according to different operative methods: autogenous bone group (34 patients, fusion with autogenous bone plus slideable pedicle screw-rod) and cage group (37 cases, fusion with cage and autogenous bone plus slideable pedicle screw-rod). The Japanese Orthopaedic Association score (JOA) and visual analogue scale (VAS) were used to assess the clinical effect postoperatively while X-ray and CT were used to evaluate the fusion situation and the height variation of fusion segment. Results The average operation time was (98.5±26.72) min in autogenous bone group, (110.4±23.41) min in cage group. All patients were followed up for 3-18 months and 5 cases were followed for more than 12 months. The height of fusion segment decreased postoperatively, however, there was no neurologic symptoms. The VAS score of low back pain and leg pain decreased by 4.7 and 6.8 points in autogenous bone group after 3 months postoperatively, it decreased by 5.1 and 6.3 points in cage group. JOA scores of 2 groups after 3 months after operation were increased by 20.8 and 19.9 points compared with preoperative scores. According to the criteria, the excellent and good rate was 91.5%. 1 case out of 5 cases followed more than 12 months can not be determined whether fusion was complete. Conclusion The novel slideable pedicle screw-rod system can provide a satisfactory outcome for the treatment of lumbar degenerative diseases and can promote the decompression segment fusion effectively. Key words: Spinal diseases; Spinal fusion; Internal fixators

Application of oblique lateral interbody fusion in the degenerative lumbar disease

Objective To investigate the operation key points and clinical efficacy of oblique lateral interbody fusion (OLIF) for the treatment of degenerative lumbar disease. Methods The clinical data of 22 patients with degenerative lumbar disease treated with OLIF at the Department of Neurosurgery, Sichuan Provincial People’s Hospital from December 2014 to October 2015 were analyzed retrospectively. Eight patients were treated with the combined posterior percutaneous pedicle screw fixation, 11 were treated with the combined anterior percutaneous pedicle screw fixation, and 3 did not treated with the screw-rod system fixation. The visual analogue scale (VAS) score, Oswestry disability index (ODI) score, and imaging findings before and after procedure were compared. The clinical efficacy of the surgical method was evaluated. The follow-up time ranged from 3 to 9 months (mean, 6.6 months). Results Postoperative VAS score (2.73±0.84) and ODI score (20.97±3.83) were significantly decreased compared with before procedure (VAS score: 7.10±0.97; ODI score: 60.86±6.88; all P<0.05). The average operation time was 92.5±14.8 min, the average blood loss was 78.4±29.6 ml, and the average length of stay was 8.2±2.4 d. Compared with before procedure, the postoperative intervertebral space height was increased (after procedure: 9.12±1.09 mm, before procedure: 5.24±1.07 mm, P<0.001) and the intervertebral foramen area was increased in 22 cases (after procedure: 1.81±0.25 cm2, before procedure: 0.83±0.10 cm2, P<0.001). None of them had severe complications, such as vascular injury, lumbar plexus nerve injury, ureteral injury and infection. Conclusions OLIF is a safe, effective, and minimally invasive surgical method for the treatment of lumbar degenerative disease. Its clinical efficacy is reliable in the near future. It has the advantages of short operation time, less intraoperative blood loss, less trauma, and quick recovery. Strict selection of patients and grasping the technical details are the keys to the success of surgery. Key words: Lumbar vertebrae; Intervertebral disc degeneration; Surgical procedures, minimally invasive; Oblique lateral interbody fusion

Generation of Induced Pluripotent Stem Cells with Substitutes for Yamanaka's Four Transcription Factors.

Induced pluripotent stem cells (iPSCs) share many characteristics with embryonic stem cells, but lack ethical controversy. They provide vast opportunities for disease modeling, pathogenesis understanding, therapeutic drug development, toxicology, organ synthesis, and treatment of degenerative disease. However, this procedure also has many potential challenges, including a slow generation time, low efficiency, partially reprogrammed colonies, as well as somatic coding mutations in the genome. Pioneered by Shinya Yamanaka's team in 2006, iPSCs were first generated by introducing four transcription factors: Oct 4, Sox 2, Klf 4, and c-Myc (OSKM). Of those factors, Klf 4 and c-Myc are oncogenes, which are potentially a tumor risk. Therefore, to avoid problems such as tumorigenesis and low throughput, one of the key strategies has been to use other methods, including members of the same subgroup of transcription factors, activators or inhibitors of signaling pathways, microRNAs, epigenetic modifiers, or even differentiation-associated factors, to functionally replace the reprogramming transcription factors. In this study, we will mainly focus on the advances in the generation of iPSCs with substitutes for OSKM. The identification and combination of novel proteins or chemicals, particularly small molecules, to induce pluripotency will provide useful tools to discover the molecular mechanisms governing reprogramming and ultimately lead to the development of new iPSC-based therapeutics for future clinical applications.

Management of Spinal Degenerative Stenosis in Patients with Spinal Tumors

Introduction The evolution of conservative treatment, such as radiation therapy, chemotherapy has prolonged significantly life expectancy of patients with spinal tumors. Paradoxically, the complexity of decision making for this patient population increased due to chronic disease management. The purpose of our research is evaluation of health-related quality of life (HRQOL) parameters in patients with spinal tumors and degenerative spinal stenosis. Material and Methods Retrospective data were collected for 17 patients with spinal tumors (multiple myeloma ( n = 7), metastasis of breast cancer ( n = 5), renal cell carcinoma ( n = 4), bladder cancer ( n = 1)). Inclusion criteria were the following: spinal tumor lesions with 0–6 scores in Spinal Instability Neoplastic Score (SINS), degenerative spinal stenosis with neurological deficit (Frankel grade C-D), unsuccessful nonoperative treatment of degenerative disease (VAS 7–9). According to revised Tokuhashi scoring system, patients were divided into two groups. The first group included 11 patients with 0–8 scores (good prognosis). The second group consisted of 6 patients with 9–11 scores (moderate prognosis). All patients underwent degenerative stenosis surgery using foraminotomy and instrumentalization. Groups were evaluated with HRQOL-scales including VAS, ODI and Frankel. HRQOL-parameters and complications were analyzed and compared between two groups. The comparisons were done by using independent sample Student t-test. A p-value of less than 0.05 was accepted as significant. Results HRQOL-scores (VAS, ODI, Frankel) of the patients were increased after operation in both groups. The HRQOL-scores after 18 months are slightly higher in the first group, but we did not get significant difference between groups (p &gt; 0.05). The number of complications in the form of implant instability, proximal and distal junctional disorders was comparable (p &gt; 0.05). No patients had progression of oncology disease or new metastasis of tumor during follow-up in the first group. In the second group tumor came out of remission in 1 case (new visceral and bone metastasis). Conclusion Management of spinal degenerative stenosis in patients with spinal tumors provides to increase quality of life. We believe that degenerative stenosis surgery does not affect on progression of oncology disease.

Oblique lumbar interbody fusion for treatment of degenerative disease of the lumbar spine: one case report

Oblique lumbar interbody fusion for treatment of degenerative disease of the lumbar spine: one case report

Shock-Wave Destruction of Tissues as a Method for Treatment of Degenerative Diseases in Gynecology

The results of research into the mechanism of the effect of shock waves on the surface structures of biological tissues are presented. Shock waves were applied to the surface structures to provide their destruction under exposure to laser radiation. The laser radiation parameters were selected so as to reduce its absorption by biological tissues. Fine particles of activated carbon with a high proportion of mesopores filled with unbound water were used to activate the shock-wave decomposition of biological tissues with minimal thermal damage. Particles were deposited on the surface of the biological tissue exposed to laser radiation. The results of histological studies of the shock-wave effect on porcine vulva skin are presented. The results obtained under otherwise identical parameters of laser radiation, but in the absence of a water suspension of fine laser-absorbing particles on the skin surface, are presented for comparison.

Protective Effect of S-Adenosyl-L-Methionine on Oxidative Stress-Induced Apoptosis Regulates Nrf-2 via IGF-I in Rat Bone Marrow Mesenchymal Stem Cells

Bone marrow mesenchymal stem cell (MSC)-mediated regeneration is a promising treatment for degenerative diseases and traumatic injuries. S-Adenosyl-L-methionine (SAM) is the principal biological methyl donor. We hypothesized that the cytoprotective effect of SAM on oxidative stress-induced apoptosis in rat MSCs is due to insulin-like growth factor-I (IGF-I) and nuclear factor erythroid 2-related factor 2 (Nrf2). SAM (10 μM) increased both endogenous IGF-I levels and cell viability (p<0.05). In MSCs, 1 mM H2O2 at 6 h significantly decreased cell viability and IGF-I and Nrf2 activation, but increased ROS generation (p<0.05 and p<0.01, respectively). The decrease in cell viability, endogenous IGF-1, and Nrf2 in H2O2-induced apoptosis was recovered by SAM (10 μM). Apoptosis induced by H2O2 also decreased Nrf2 activity, as determined by immunofluorescence staining, but the decrease was also recovered by SAM. We demonstrated that H2O2-induced apoptosis was reduced by SAM through Annexin-V. Using a specific small interfering RNA (siRNA), the increase in SAM-induced cell viability and endogenous Nrf2 in the presence of H2O2 was suppressed by IGF-I siRNA, but the endogenous IGF-I level was not changed by Nrf2 siRNA. The increase in endogenous Nrf2 with exogenous IGF-I and H2O2 treatment was also suppressed by Nrf2 siRNA, but the IGF-I level was not inhibited (p<0.05). These results suggest that the cytoprotective effect of SAM against H2O2- induced apoptosis is mediated by increased Nrf2 activity through IGF-I. These factors could regulate the metabolic fate and survival of MSCs

Medical ozone therapy as a potential treatment modality for regeneration of damaged articular cartilage in osteoarthritis.

Osteoarthritis (OA) is the most common degenerative joint disease and a growing health problem affecting more than half of the population over the age of 65. It is characterized by inflammation in the cartilage and synovium, resulting in the loss of joint structure and progressive damage to the cartilage. Many pro-inflammatory mediators are elevated in OA, including reactive oxygen species (ROS) such as nitric oxide (NO) and hydrogen peroxide (H2O2). Damaged articular cartilage remains a challenge to treat due to the limited self-healing capacity of the tissue and unsuccessful biological interventions. This highlights the need for better therapeutic strategies to heal damaged articular cartilage. Ozone (O3) therapy has been shown to have positive results in the treatment of OA; however the use of O3 therapy as a therapeutic agent is controversial. There is a perception that O3 is always toxic, whereas evidence indicates that when it is applied following a specified method, O3 can be effective in the treatment of degenerative diseases. The mechanism of action of O3 therapy in OA is not fully understood and this review summarizes the use of O3 therapy in the treatment of damaged articular cartilage in OA.

Dopaminergic-primed fetal liver mesenchymal stromal–like cells can reverse parkinsonian symptoms in 6-hydroxydopamine-lesioned mice

Background aimsCell replacement therapy is considered a promising alternative in the treatment of degenerative diseases, and in this context, mesenchymal stromal cells (MSCs) have been proposed for transplantation in Parkinson disease (PD). Thus far, the results of animal studies are found to be inconsistent and inconclusive regarding the therapeutic ability of the cells. This study investigated the efficacy of fetal liver (FL)-MSC-derived dopaminergic (DA) neuronal primed cells for correction of parkinsonian symptoms in mice. MethodsFL-MSCs were differentiated for 21 days in the presence of a combination of neurotropic factors. The extent of cellular reprogramming was analyzed by quantitative polymerase chain reaction for DA-specific neuronal gene expressions and protein expressions by immuno-cytochemistry. The functionality of the cells was determined by electrophysiology and dopamine release assays. Ten-day-primed neuron-like cells or unprimed MSCs were transplanted into the 6-hydroxydopamine (6-OHDA)-lesioned striatum using a stereotaxic device. Dopamine-secreting properties and behavioral studies were used to assess improvement of parkinsonian symptoms. ResultsThe differentiated cells expressed DA-specific genes and proteins, while exhibiting a high level of voltage-gated potassium current. Furthermore, neuronal primed cells differentiated into tyrosine hydroxylase immunoreactive and dopamine-secreting functional neuron-like cells. Symptomatic correction of PD in the recipient mice within 2 months of transplantation was also observed. DiscussionFL-MSC-derived primed neuron-like cells integrated into the striatum of PD mice, improving parkinsonian symptoms. This study demonstrates an effective cell-based therapy for PD.