Injection Of Mesenchymal Stem Cells Research Articles

Clinical safety of computed tomography-guided injection of autologous muscle-derived mesenchymal stem cells in the intervertebral disc in dogs.

Background: Pre-clinical randomized controlled animal trials have been conducted to evaluate the effect of mesenchymal stem cell (MSCs) transplantation on intervertebral disc (IVD) degeneration. MSCs can be obtained from different tissues, but systematic studies concerning the effects of muscle-derived MSCs injections on canine naturally degenerated IVD are still lacking. The aim of this study is the assessment of the clinical safety of this technique and its effects on the imaging features of the lumbosacral IVD. Methods: Eight adult healthy Beagle dogs were used in this study. In the preliminary phase, viability of muscle-derived MSCs in presence of contrast medium was assessed. In the clinical assessment phase, MSCs were injected in the lumbosacral IVD by computed-tomography (CT) guidance, after the injection of contrast medium to assess the correct intradiscal needle position. Regular clinical examinations were performed and pre- and post-injections (CT) and magnetic resonance imaging (MRI) features of the IVD were assessed. Results: The percentage of viability of MSCs in the presence of contrast medium ranged from 90 to 98%. 3x106 MSCs were obtained from six dogs and injected in the IVD. No major or minor complications were reported during the procedure and no abnormalities were noticed during the clinical examinations. No statistically significant variations were noticed between the pre- and post-injections imaging features. Conclusion: This technique is clinically safe and it is not associated with any progression of the IVD degeneration, detected by CT and MRI imaging.

Mesenchymal stem cells after the proprocessing of tanshinone IIA attenuate cognitive deficits and oxidative stress injury in an amyloid β-peptide (25-35)-induced rodent model of Alzheimer's disease.

To verify whether mesenchymal stem cells cocultured with tanshinone IIA may ameliorate Alzheimer's disease by inhibiting oxidative stress. Sixty male Sprague-Dawley rats were randomly divided into 4 groups named Sham, Aβ25-35, mesenchymal stem cells, and mesenchymal stem cells (tanshinone IIA). The rats were treated according to different groups. The neurobehavioral performance of Sprague-Dawley rats was evaluated via Morris water maze test. Histological changes were checked via hematoxylin-eosin staining. The levels of total antioxidant activity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and malondialdehyde in hippocampus were assayed by ELISA kit. The levels of Aβ, p-tau/tau, and p-AMP-activated protein kinase/AMP-activated protein kinase in hippocampus were checked by Western blot. Our research showed that the injection of mesenchymal stem cells (tanshinone IIA) into the hippocampus alleviated learning and memory deficits and reduced hippocampal neuronal injury in the Alzheimer's disease rats. Moreover, mesenchymal stem cells (tanshinone IIA) treatment suppressed oxidative stress, attenuated Aβ accumulation reduced Tau hyperphosphorylation, and enhanced the activity of AMP-activated protein kinase in the hippocampus of the Alzheimer's disease rats. However, there were almost no significant difference between the mesenchymal stem cells and Aβ25-35 groups. Mesenchymal stem cells (tanshinone IIA) transplantation may be a potential treatment for curing Alzheimer's disease, which may be related to the inhibition of oxidative stress.

Bone marrow derived-mesenchymal stem cell improves diabetes-associated fatty liver via mitochondria transformation in mice

BackgroundNon-alcoholic fatty liver disease (NAFLD) has become a global epidemic disease. Its incidence is associated with type 2 diabetes mellitus (T2DM). Presently, there is no approved pharmacological agents specially developed for NAFLD. One promising disease-modifying strategy is the transplantation of stem cells to promote metabolic regulation and repair of injury.MethodIn this study, a T2DM model was established through 28-week high-fat diet (HFD) feeding resulting in T2DM-associated NAFLD, followed by the injection of bone marrow mesenchymal stem cells (BMSCs). The morphology, function, and transfer of hepatocyte mitochondria were evaluated in both vivo and in vitro.ResultsBMSC implantation resulted in the considerable recovery of increasing weight, HFD-induced steatosis, liver function, and disordered glucose and lipid metabolism. The treatment with BMSC transplantation was accompanied by reduced fat accumulation. Moreover, mitochondrial transfer was observed in both vivo and vitro studies. And the mitochondria-recipient steatotic cells exhibited significantly enhanced OXPHOS activity, ATP production, and mitochondrial membrane potential, and reduced reactive oxygen species levels, which were not achieved by the blocking of mitochondrial transfer.ConclusionMitochondrial transfer from BMSCs is a feasible process to combat NAFLD via rescuing dysfunction mitochondria, and has a promising therapeutic effect on metabolism-related diseases.

Effects of Mesenchymal Stem Cell Transplantation in Combination with Heparin on Acute Myocardial Infarction in a Rabbit Model

Background and Aim: Background: Stem cell transplantation, combined with some bioactive substances, has revealed promising outcomes in treating cardiac tissue damage caused by myocardial infarction (MI). In the present study, we evaluated the beneficial consequence of mesenchymal stem cells (MSCs) transplantation combined with heparin on heart damage within infarcted rabbits. Methods: Twenty-eight male New Zealand white rabbits were randomly distributed into four groups: control, MI, MI+ MSCs, and MI+MSCs+ heparin. Functional parameters of the left ventricle through echocardiography, lesion area through Macro trichrome evaluation, and angiogenesis through Masson's trichrome staining were compared between groups. Results: Ejection fraction and fractional shortening were improved in MI +MSCs and MI+ MSCs + heparin group compared to the MI group (P<0.05). The lesion area was significantly reduced, and angiogenesis was markedly increased in MI +MSC + heparin treated animals compared to MI and MI +MSCs groups. Conclusion: Although MSCs injection to infarcted area restored normal heart function, we concluded that in the infarcted region of animals, MSCs injection combined with exogenous heparin could have more effects on the left ventricle functional parameters, cardiac lesions, and new vessel formation. *Corresponding Author: Roya Khosh Ravesh; Email: Khoshraveshroya82@gmail.com Please cite this article as: Hajigol S, Moradi Gardeshi T, Safizadeh F, Khosh Ravesh R, Abbasi M. Effects of Mesenchymal Stem Cell Transplantation in Combination with Heparin on Acute Myocardial Infarction in a Rabbit Model. Arch Med Lab Sci. 2021;7:1-9 (e19). https://doi.org/10.22037/amls.v7.34932

Abstract 12993: Administration of Echogenic Immunoliposome-Targeted CD146 + Mesenchymal Stem Cells Reduces Hypercholesterolemia and Atherosclerosis

Introduction and Hypothesis: Mesenchymal stem cells (MSC) have been used to treat atherosclerosis and diabetes in animal studies and clinical trials. We developed a nanotechnology in which MSC can be targeted with anti-CD146/ICAM bifunctional (BF) echogenic immunoliposomes (ELIP) for treatment of atherosclerosis. Here, we tested the hypothesis that BF-ELIP targeted MSC therapy is biologically safe and effective for preventing hypercholesterolemia and atheroma. Methods and Results: BF-ELIP with antibodies to the mesenchymal marker CD146 and the adhesion protein ICAM-1 were mixed with CD146 + MSC grown from adipose tissue of green fluorescence protein (GFP)-transgenic mice. The BF-ELIP/MSC mixtures or controls, such as non-immune ELIP (NE)/MSC mixtures, NE and MSC alone, were intravenously administered to C57BL/6J wild type (WT) and apolipoprotein-E deficient (ApoE -/- ) mice, which were age-/sex-matched. In a nearly 4 months followup, all the mice survived the ELIP/MSC injection without major adverse effects observed. No major difference in blood pressure was found between ELIP/MSC-treated and non-MSC controls. Total cholesterol and glucose were examined in blood samples collected from the animals. ApoE -/- mice developed significantly higher cholesterol (p&lt;0.05) but lower glucose (p&lt;0.05) levels than WT mice. The BF-ELIP targeted MSC injection reduced levels of total cholesterol and, to a lesser extent, glucose (p&lt;0.05). Non-invasive ultrasound confirmed enhancement of ELIP echogenicity and imaging of atheroma. Fluorescence microscopy illustrated GFP expression in the MSC mixtures and the arterial wall with atheroma. H&amp;E and Oil-Red O staining showed reduced plaque formation and lipid loading in the arterial wall of ApoE -/- but not WT mice with the MSC delivery. Conclusions: Administration of BF-ELIP targeted MSCs appears to be a safe, effective procedure, which may mitigate hypercholesterolemia and atherogenesis.

Injectable xyloglucan hydrogels incorporating spheroids of adipose stem cells for bone and cartilage regeneration

Cartilage or bone regeneration approaches based on the direct injection of mesenchymal stem cells (MSCs) at the lesion site encounter several challenges, related to uncontrolled cell spreading and differentiation, reduced cell viability and poor engrafting. This work presents a simple and versatile strategy based on the synergic combination of in-situ forming hydrogels and spheroids of adipose stem cells (SASCs) with great potential for minimally invasive regenerative interventions aimed to threat bone and cartilage defects. Aqueous dispersions of partially degalactosylated xyloglucan (dXG) are mixed with SASCs derived from liposuction and either a chondroinductive or an osteoinductive medium. The dispersions rapidly set into hydrogels when temperature is brought to 37 °C. The physico-chemical and mechanical properties of the hydrogels are controlled by polymer concentration. The hydrogels, during 21 day incubation at 37 °C, undergo significant structural rearrangements that support cell proliferation and spreading. In formulations containing 1%w dXG cell viability increases up to 300% for SASCs-derived osteoblasts and up to 1000% for SASCs-derived chondrocytes if compared with control 2D cultures. The successful differentiation into the target cells is supported by the expression of lineage-specific genes. Cell-cell and cell-matrix interactions are also investigated. All formulations resulted injectable, and the incorporated cells are fully viable after injection.

Injectable therapies for knee osteoarthritis

Knee osteoarthritis is a degenerative arthritis that mainly affects older adults. Over time, osteoarthritis can result in significant and sustained discomfort, pain, and disability. Current treatment focuses on the alleviation of pain and functional impairment. While arthroplasty is the definitive management option, it subjects patients to surgical complications, and the possibility of surgical revisions. In addition, many patients are not surgical candidates. Instead, pharmacological therapy is recommended first-line for most patients. On top of pharmacological therapy, there are a range of non-operative procedural options available. However, leading professional guidelines vary in their recommendations for these agents.Therefore, we present a review of recent randomized controlled trials and meta-analyses on injectable corticosteroids, hyaluronic acid (HA), platelet-rich plasma (PRP), mesenchymal stem cell injections, and ozone therapy. The preliminary data reveal the strongest evidence in favour of corticosteroid injections, although there are promising findings regarding the long-term efficacy of HA and PRP.

The potential of platelet-rich plasma injections and stem cell therapy for penile rejuvenation.

Penile concerns include erectile dysfunction (ED) and Peyronie disease (PD). Restorative therapies including Stem Cell Therapy (SCT) and Platelet Rich Plasma (PRP) injections are proposed to treat these concerns. SCT encompasses the harvesting and injection of mesenchymal stem cells or stromal vascular fractions from various tissue sources. PRP is derived autologously from a patient's plasma and is then injected into the penile tissue. These therapies repair damaged penile tissue and promote both new cellular and vascular growth, as demonstrated in basic science studies. Human trials on SCT and PRP for both ED and PD and have yielded promising results with few side effects. While encouraging, small cohort size and lack of blinding or placebo control limit these studies' external validity. Recently, the first double-blinded randomized controlled trial on PRP for ED was published, providing significant evidence of efficacy. With the rapid commercial availability of SCT and PRP for ED and PD, it is imperative to perform more randomized and placebo-controlled trials with standardized procedures and preparations to evaluate efficacy and safety. This narrative review will summarize the available literature on these penile restorative therapies to date.

Current Clinical Application of Mesenchymal Stem Cells in the Treatment of Severe COVID-19 Patients: Review.

Coronavirus-2019 disease is a newly diagnosed infectious disease, which is caused by the severe acute respiratory syndrome corona virus-2. It spreads quickly and has become a major public health problem throughout the world. When the viral structural spike protein binds to the angiotensin-converting enzyme-2 receptor of the host cell membrane, the virus enters into host cells. The virus primarily affects lung epithelial cells or other target cells that express angiotensin-converting enzyme-2 receptors in COVID-19 patients. Chemokines released by the host cells stimulate the recruitment of different immune cells. A cytokine storm occurs when a high amount of pro-inflammatory cytokines are produced as a result of the accumulation of immune cells. In COVID-19 patients, cytokine storms are the leading cause of severe acute respiratory distress syndrome. Mesenchymal stem cells are multipotent and self-renewing adult stem cells, which are obtained from a variety of tissues including bone marrow, adipose tissue, Warthon’s jelly tissue, and amniotic fluid. Mesenchymal stem cells primarily exert their important therapeutic effects through 2 mechanisms: immunoregulatory effects and differentiation capacity. Mesenchymal stem cells can release several cytokines via paracrine mechanism or by direct interaction with white blood cells such as natural killer cells, T-lymphocytes, B-lymphocytes, natural killer cells, and macrophages, resulting in immune system regulation. Mesenchymal stem cells may help to restore the lung microenvironment, preserve alveolar epithelial cells, prevent lung fibrosis, and treat pulmonary dysfunction that is caused by COVID-19 associated pneumonia. Mesenchymal stem cells therapy may suppress aggressive inflammatory reactions and increase endogenous restoration by improving the pulmonary microenvironment. Furthermore, clinical evidence suggests that intravenous injection of mesenchymal stem cells may radically reduce lung tissue damage in COVID-19 patients. With the advancement of research involving mesenchymal stem cells for the treatment of COVID-19, mesenchymal stem cells therapy may be the main strategy for reducing the recent pandemic.

Bone Marrow-Derived Mesenchymal Stem Cells Augment Regeneration of Intervertebral Disc in a Reproducible and Validated Mouse Intervertebral Disc Degeneration Model.

Back pain and radicular pain due to disc degeneration are probably the most common problems encountered in neurosurgical practice. The experience and results of stem cell therapy in animal disc degeneration model will help us while doing clinical trials. To study the effect of bone marrow-derived mesenchymal stem cells in an established mouse disc degeneration model. An easily reproducible mouse coccygeal (Co) 4-5 disc degenerated model by CT-guided percutaneous needle injury was established. The mesenchymal stem cells (MSCs) were cultured from mouse bone marrow and validated. By an established technique, 24 mice disc degenerative models were generated and divided equally into 3 groups (test, placebo, and control). The test group received MSCs with fibrin glue scaffold and placebo group received only scaffold after 6 weeks of degeneration. The control group did not receive any injection. The effects of MSCs were analyzed 8 weeks post injection. The test group showed a significant change in disc height index (%) in micro CT, whereas in the placebo and control groups, there was no change. The Safranin O staining showed an increase in glycosaminoglycan content and the polarized imaging of picrosirius red staining showed restoration of the collagen fibers in annulus fibrosus, which was statistically significant. Intradiscal MSC injection restored disc height and promoted regeneration in the discs at the end of 8 weeks. MSC's niche depends on the microenvironment of the host tissue. These findings will be helpful for clinical trials.

Transplant of Autologous Mesenchymal Stem Cells Halts Fatty Atrophy of Detached Rotator Cuff Muscle After Tendon Repair: Molecular, Microscopic, and Macroscopic Results From an Ovine Model

Background: The injection of mesenchymal stem cells (MSCs) mitigates fat accumulation in released rotator cuff muscle after tendon repair in rodents. Purpose: To investigate whether the injection of autologous MSCs halts muscle-to-fat conversion after tendon repair in a large animal model for rotator cuff tendon release via regional effects on extracellular fat tissue and muscle fiber regeneration. Study Design: Controlled laboratory study. Methods: Infraspinatus (ISP) muscles of the right shoulder of Swiss Alpine sheep (n = 14) were released by osteotomy and reattached 16 weeks later without (group T; n = 6) or with (group T-MSC; n = 8) electropulse-assisted injection of 0.9 Mio fluorescently labeled MSCs as microtissues with media in demarcated regions; animals were allowed 6 weeks of recovery. ISP volume and composition were documented with computed tomography and magnetic resonance imaging. Area percentages of muscle fiber types, fat, extracellular ground substance, and fluorescence-positive tissue; mean cross-sectional area (MCSA) of muscle fibers; and expression of myogenic (myogenin), regeneration (tenascin-C), and adipogenic markers (peroxisome proliferator-activated receptor gamma [PPARG2]) were quantified in injected and noninjected regions after recovery. Results: At 16 weeks after tendon release, the ISP volume was reduced and the fat fraction of ISP muscle was increased in group T (137 vs 185 mL; 49% vs 7%) and group T-MSC (130 vs 166 mL; 53% vs 10%). In group T-MSC versus group T, changes during recovery after tendon reattachment were abrogated for fat-free mass (–5% vs –29%, respectively; P = .018) and fat fraction (+1% vs +24%, respectively; P = .009%). The area percentage of fat was lower (9% vs 20%; P = .018) and the percentage of the extracellular ground substance was higher (26% vs 20%; P = .007) in the noninjected ISP region for group T-MSC versus group T, respectively. Regionally, MCS injection increased tenascin-C levels (+59%) and the water fraction, maintaining the reduced PPARG2 levels but not the 29% increased fiber MCSA, with media injection. Conclusion: In a sheep model, injection of autologous MSCs in degenerated rotator cuff muscle halted muscle-to-fat conversion during recovery from tendon repair by preserving fat-free mass in association with extracellular reactions and stopping adjuvant-induced muscle fiber hypertrophy. Clinical Relevance: A relatively small dose of MSCs is therapeutically effective to halt fatty atrophy in a large animal model.

Intramuscular injection of mesenchymal stem cells activates anabolic and catabolic systems in mouse skeletal muscle

Skeletal muscle mass is critical for good quality of life. Mesenchymal stem cells (MSCs) are multipotent stem cells distributed across various tissues. They are characterized by the capacity to secrete growth factors and differentiate into skeletal muscle cells. These capabilities suggest that MSCs might be beneficial for muscle growth. Nevertheless, little is known regarding the effects on muscle protein anabolic and catabolic systems of intramuscular injection of MSCs into skeletal muscle. Therefore, in the present study, we measured changes in mechanistic target of rapamycin complex 1 (mTORC1) signaling, the ubiquitin–proteasome system, and autophagy-lysosome system-related factors after a single intramuscular injection of MSCs with green fluorescence protein (GFP) into mouse muscles. The intramuscularly-injected MSCs were retained in the gastrocnemius muscle for 7 days after the injection, indicated by detection of GFP and expression of platelet-derived growth factor receptor-alpha. The injection of MSCs increased the expression of satellite cell-related genes, activated mTORC1 signaling and muscle protein synthesis, and increased protein ubiquitination and autophagosome formation (indicated by the expression of microtubule-associated protein 1 light chain 3-II). These results suggest that the intramuscular injection of MSCs activated muscle anabolic and catabolic systems and accelerated muscle protein turnover.

Comparison of the Effects of Intratubal Injection of Adipose-Derived Mesenchymal Stem Cells in a Rat Sciatic Nerve Transection: An Experimental Study.

This study was designed to evaluate the efficacy of epineural tubulization (ENT) with or without intratubal application of adipose-derived mesenchymal stem cells (ASCs) in the rat model of sciatic nerve transection. After formation of 1-cm defect in the left sciatic nerve and ENT, 32 adults female Wistar albino rats were separated into 4 groups (n = 8 for each) including ENT per se (group 1; ENT group) and ENT plus intratubal ASC injection groups killed on day 21 (group 2; ENT-ASC-21-day group), 60 days (group 3; ENT-ASC-60-day group), and 120 days (group 4; ENT-ASC-120-day group). Functional (sciatic function index, hip circumference, withdrawal reflex latency, muscle weight ratio), electrophysiological, histomorphometric, and immunohistochemical analyses were performed in each group. Sciatic function index was significantly higher (-51.98 ± 5.94, P < 0.01) and withdrawal reflex latency was shorter (-6.21 ± 2.14, P < 0.01), in the group 4 as compared with all other groups on day 21. Amplitude of contraction was significantly lower in the group 4 as compared with all other groups (0.22 ± 0.05 vs 0.34 ± 0.07, 0.50 ± 0.11, and 0.61 ± 0.16, P < 0.01 for each). Immunohistochemical analysis revealed presence of green fluorescent protein, vimentin-stained cells, and single neural progenitor cells indicating that induction of neuronal differentiation by ASCs and direct involvement of ASCs within the axonal structure alongside extension of ASCs to the muscular layer of the group 4. In conclusion, our findings revealed that use of ENT plus intratubal ASC injection in a rat sciatic nerve transection model was associated with satisfactory functional outcome and improved peripheral axonal regeneration along with stem cell neural differentiation.

Combining systemic and locally applied cellular therapies for the treatment of systemic sclerosis.

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by a functional and structural alteration of the microvascular network associated with cutaneous and visceral fibrosis lesions. Conventional therapies are based on the use of immunomodulatory molecules and symptomatic management but often prove to be insufficient, particularly for patients suffering from severe and rapidly progressive forms of the disease. In this context, cellular therapy approaches could represent a credible solution with the goal to act on the different components of the disease: the immune system, the vascular system and the extracellular matrix. The purpose of this review is to provide an overview of the cellular therapies available for the management of SSc. The first part will focus on systemically injected therapies, whose primary effect is based on immunomodulatory properties and immune system resetting, including autologous hematopoietic stem cell transplantation and intravenous injection of mesenchymal stem cells. The second part will discuss locally administered regenerative cell therapies, mainly derived from adipose tissue, developed for the management of local complications as hand and face disabilities.

SDF-1 secreted by mesenchymal stem cells promotes the migration of endothelial progenitor cells via CXCR4/PI3K/AKT pathway

Cell-based therapeutics bring great hope in areas of unmet medical needs. Mesenchymal stem cells (MSCs) have been suggested to facilitate neovascularization mainly by paracrine action. Endothelial progenitor cells (EPCs) can migrate to ischemic sites and participate in angiogenesis. The combination cell therapy that includes MSCs and EPCs has a favorable effect on ischemic limbs. However, the mechanism of combination cell therapy remains unclear. Herein, we investigate whether stromal cell-derived factor (SDF)-1 secreted by MSCs contributes to EPC migration to ischemic sites via CXCR4/Phosphoinositide 3-Kinases (PI3K)/protein kinase B (termed as AKT) signaling pathway. First, by a "dual-administration" approach, intramuscular MSC injections were supplemented with intravenous Qdot® 525 labeled-EPC injections in the mouse model of hind limb ischemia. Then, the mechanism of MSC effect on EPC migration was detected by the transwell system, tube-like structure formation assays, western blot assays in vitro. Results showed that the combination delivery of MSCs and EPCs enhanced the incorporation of EPCs into the vasculature and increased the capillary density in mouse ischemic hind limb. The numbers of CXCR4-positive EPCs increased after incubation with MSC-conditioned medium (CM). MSCs contributed to EPC migration and tube-like structure formation, both of which were suppressed by AMD3100 and wortmannin. Phospho-AKT induced by MSC-CM was attenuated when EPCs were pretreated with AMD3100 and wortmannin. In conclusion, we confirmed that MSCs contributes to EPC migration, which is mediated via CXCR4/PI3K/AKT signaling pathway.

Development of injectable graphene oxide/laponite/gelatin hydrogel containing Wharton's jelly mesenchymal stem cells for treatment of oxidative stress-damaged cardiomyocytes

In the initial stage of myocardial infarction (MI), cardiomyocyte necrosis activates aninflammatory response and increases the reactive oxygen species (ROS) content. Graphene oxide (GO) possesses potential antioxidant properties and can provide the adequate mechanical support for cell growth. The clinical studies showed that direct injection of Wharton's jelly mesenchymal stem cells (WJ-MSCs) into infarcted areas of myocardium can reduce apoptosis and fibrosis. Gelatin is a natural polymer and can promote cell attachment. Nanoclay laponite with shear-thinning properties can be injected and gelled in-situ without chemical triggers. In the study, injectable GO/laponite/gelatin (GO-LG) hydrogel was developed and characterized. The results of cell viability showed that the optimal concentration of GO flasks (200 to 300 nm) to treat cells was 100 μg/ml. Addition of nanosized GO to the laponite/gelatin (LG) hydrogel could increase the mechanical strength and have both hemocompatibility and cytocompatibility. The release of GO from LG hydrogel could inhibit the H2O2-induced oxidative stress. The GO-LG hydrogel containing WJ-MSCs could decrease inflammation and apoptosis level and increase the cell viability of cardiomyocytes under oxidative stress. We believe that utilizing this newly developed GO-LG hydrogel containing WJ-MSCs may have potential applications in the future for treatment of MI.

Clinical outcomes following intra-articular injection of autologous adipose-derived mesenchymal stem cells for the treatment of osteoarthritis in dogs characterized by weight-bearing asymmetry.

AimsThis study investigates the effects of intra-articular injection of adipose-derived mesenchymal stem cells (AdMSCs) and platelet-rich plasma (PRP) on lameness, pain, and quality of life in osteoarthritic canine patients.MethodsWith informed owner consent, adipose tissue collected from adult dogs diagnosed with degenerative joint disease was enzymatically digested and cultured to passage 1. A small portion of cells (n = 4) surplus to clinical need were characterized using flow cytometry and tri-lineage differentiation. The impact and degree of osteoarthritis (OA) was assessed using the Liverpool Osteoarthritis in Dogs (LOAD) score, Modified Canine Osteoarthritis Staging Tool (mCOAST), kinetic gait analysis, and diagnostic imaging. Overall, 28 joints (25 dogs) were injected with autologous AdMSCs and PRP. The patients were followed up at two, four, eight, 12, and 24 weeks. Data were analyzed using two related-samples Wilcoxon signed-rank or Mann-Whitney U tests with statistical significance set at p < 0.05.ResultsAdMSCs demonstrated stem cell-like characteristics. LOAD scores were significantly lower at week 4 compared with preinjection (p = 0.021). The mCOAST improved significantly after three months (p = 0.001) and six months (p = 0.001). Asymmmetry indices decreased from four weeks post-injection and remained significantly lower at six months (p = 0.025).ConclusionThese improvements in quality of life, reduction in pain on examination, and improved symmetry in dogs injected with AdMSCs and PRP support the effectiveness of this combined treatment for symptom modification in canine OA for six months.Cite this article: Bone Joint Res 2021;10(10):650–658.

Administration of Autologous Mesenchymal Cells for the Treatment of Arthritis.

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. A PubMed literature search was performed to identify adverse events specifically related to the injection of autologous mesenchymal or hematopoietic stem cells into arthritic joints or intravenously. 2,011 reported injections were found. No stem cell specific adverse events were identified. Specifically no infections, tumorigenesis, or chondrolysis from collagenase were found. Intra-articular injection of autologous mesenchymal stem cells for the treatment of arthritis is completely safe with no stem cell specific adverse events yet documented, and no increased risk compared with other traditional treatments for arthritis.

Conservative Treatment of Ankle Osteoarthritis.

Despite the disabling nature of ankle osteoarthritis (OA), there is poor scientific evidence for a conservative treatment compared to the hip and knee OA. In this regard, most of the treatment options in use are not based on clinical studies of the ankle, and they are extracted from evidence obtained from clinical studies of other lower limb joints. However, this does not seem to be a good idea, since the aetiology of ankle OA is quite different from that of the hip or knee. Nonpharmacological and pharmacological treatments such as nonsteroidal anti-inflammatory drugs, hyaluronic acid, corticosteroid, platelet-rich plasma injection and mesenchymal stem cells injections have been reported. However, further research is required in this field to obtain a specific clinical practice guideline for the conservative treatment of ankle OA.

AD-MSCs and BM-MSCs Ameliorating Effects on The Metabolic and Hepato-renal Abnormalities in Type 1 Diabetic Rats

Diabetes mellitus (DM) is one of the most serious threats in the 21th century throughout the human population that needs to be addressed cautiously. Nowadays, stem cell injection is considered among the most promising protocols for DM therapy; owing to its marked tissues and organs repair capability. Therefore, our 4 weeks study was undertaken to elucidate the probable beneficial effects of two types of adult mesenchymal stem cells (MSCs) on metabolism disturbance and some tissue function defects in diabetic rats. Animals were classified into 4 groups; the control group, the diabetic group, the diabetic group received a single dose of adipose tissue-derived MSCs and the diabetic group received a single dose of bone marrow-derived MSCs. Herein, both MSCs treated groups markedly reduced hyperglycemia resulting from diabetes induction via lowering serum glucose and rising insulin and C-peptide levels, compared to the diabetic group. Moreover, the increased lipid fractions levels were reverted back to near normal values as a consequence to MSCs injection compared to the diabetic untreated rats. Furthermore, both MSCs types were found to have hepato-renal protective effects indicated through the decreased serum levels of both liver and kidney functions markers in the treated diabetic rats. Taken together, our results highlighted the therapeutic benefits of both MSCs types in alleviating metabolic anomalies and hepato-renal diabetic complications.