Allogenic Pure Platelet-Rich Plasma Therapy for Adhesive Capsulitis: A Bed-to-Bench Study With Propensity Score Matching Using a Corticosteroid Control Group

2021 ◽  
pp. 036354652110186
Author(s):  
Min Ji Lee ◽  
Kang Sup Yoon ◽  
Sohee Oh ◽  
Sue Shin ◽  
Chris Hyunchul Jo

Background: While platelet-rich plasma (PRP) has been widely studied for musculoskeletal disorders, few studies to date have reported its use for adhesive capsulitis (AC). Fully characterized and standardized allogenic PRP may provide clues to solve the underlying mechanism of PRP with respect to synovial inflammation and thus may clarify its clinical indications. Purpose: To clinically evaluate the safety and efficacy of a fully characterized pure PRP injection in patients with AC and to assess the effects of pure PRP on synoviocytes with or without inflammation in vitro. Study Design: Controlled laboratory study and cohort study; Level of evidence, 3. Methods: For the clinical analysis, a total of 15 patients with AC received an ultrasonography-guided intra-articular PRP injection and were observed for 6 months. Pain, range of motion (ROM), muscle strength, shoulder function, and overall satisfaction in the patients were evaluated using questionnaires at 1 week as well as at 1, 3, and 6 months after the PRP injection and results were compared with the results of a propensity score−matched control group that received a corticosteroid injection (40 mg triamcinolone acetonide). For the in vitro analysis, synoviocytes were cultured with or without interleukin-1β (IL-1β) and PRP. The gene expression of proinflammatory and anti-inflammatory cytokines as well as matrix enzymes and their inhibitors was evaluated. Results: At 6-month follow-up, pure PRP significantly decreased pain and improved ROM, muscle strength, and shoulder function to levels comparable with those after a corticosteroid injection. All pain values, strength measurements, and functional scores significantly improved up to 6 months in the PRP group, but these measures improved up to 3 months and then were decreased at 6 months in the corticosteroid group. ROM was significantly improved in the 2 groups at 6 months compared with baseline. Allogenic PRP did not cause adverse events. For the in vitro findings, PRP induced inflammation but significantly improved the IL 1β−induced synovial inflammatory condition by decreasing proinflammatory cytokines such as IL-1β, tumor necrosis factor−α, IL-6, cyclooxygenase-2, and microsomal prostaglandin E synthase−1 and decreased matrix enzymes (matrix metalloproteinase−1, −3, and −13 as well as a disintegrin and metalloproteinase with thrombospondin motifs−4 and −5) and further increasing anti-inflammatory cytokines such as vasoactive intestinal peptide. Conclusion: This study showed that PRP decreased pain and improved shoulder ROM and function to an extent comparable with that of a corticosteroid in patients with AC. Allogenic pure PRP acted in a pleiotropic manner and decreased proinflammatory cytokines only in the inflammatory condition. Clinical Relevance: Allogenic PRP could be a treatment option for the inflammatory stage of AC.

1987 ◽  
Author(s):  
J De Crée ◽  
H Geukens ◽  
H Demoen ◽  
H Verhaegen

Red blood cell (RBC) filtration in platelet rich plasma (PRP) and platelet poor plasma (PPP) was equally decreased (p < 0.0001) in 120 patients with acute myocardial infarction (AMI) as compared to a control group. In a double-blind experiment 2 groups of 30 patients with AMI received an acute oral dose of 60 mg of ketanserin, a serotonin (5-HT) antagonist at 5-HT2-receptors, or placebo. Ketanserin treatment improved RBC filtration in PRP with an average increase of 30%. A similar experiment using PPP showed a significant increase of 10%. Filtration of plasma improved after ketanserin treatment in PRP, but not in PPP. Cross-exchange experiments showed the ketanserin-induced improvement of RBC filtration in PRP and PPP to be also plasmadependent. 5-HT in vitro at 10−9M deteriorated RBC filtration in PPP (p < 0.05), and ketanserin in vitro at 10−7M counteracted this phenomenon (p < 0.001). Finally we found that the effect of a subacute treatment with ketanserin on the filtration of RBC Suspensions, enriched with a constant amount of white blood cells (WBC), was more pronounced than on control RBC suspensions of patients with AMI.These results indicate that the impaired RBC filtration, reported in vascular diseases may be dependent on a subtle interaction between platelets, WBC, RBC and plasma. Treatment with ketanserin is capable to interrupt this vicious circle of rheological disturbances at different levels, first of all, by improving RBC deformability, but also by counteracting the platelet mediated effects on RBC and by favourably influencing the physical properties of WBC and so preventing clogging phenomena. Serotonin probably plays a pivotal role in these cascade of events and therapy with ketanserin might be of clinical value in diseases where microcirculatory flow is compromised.


2004 ◽  
Vol 92 (07) ◽  
pp. 89-96 ◽  
Author(s):  
David Payne ◽  
Chris Jones ◽  
Paul Hayes ◽  
Sally Webster ◽  
A. Naylor ◽  
...  

SummaryThe majority of patients who suffer peri-operative thromboembolic complication while undergoing vascular procedures do so despite taking aspirin. This study examined the antiplatelet effect of aspirin during surgery in patients undergoing carotid endarterectomy (CEA). Fifty patients undergoing CEA were standardised to 150 mg aspirin daily for ≥2 weeks. Platelet aggregation in response to arachidonic acid (AA) was measured in platelet rich plasma prepared from blood taken prior to, during, and at the end of surgery. Spontaneous platelet aggregation was also studied, as was the role of physiological agonists (ADP, collagen, thrombin, and epinephrine) in mediating the in vivo and in vitro responses to AA. Eighteen patients undergoing leg angioplasty, also on 150 mg aspirin, without general anaesthesia, served as a control group. In the CEA patients aggregation induced by AA (5 mM) increased significantly from 7.6 ± 5.5% pre-surgery to 50.8 ± 29.5% at the end of surgery (p <0.0001). Aggregation to AA was even greater in samples taken mid-surgery from a sub-set of patients (73.8 ± 7.2%; p = 0.0001), but fell to 45.9 ± 7.4% by the end of surgery. The increased aggregation in response to AA was not due to intra-operative release of physiological platelet agonists since addition of agents that block/neutralise the effects of ADP (apyrase; 4 µg/ml), thrombin (hirudin; 10 units/ml), or epinephrine (yohimbine; 10 µM/l) to the samples taken at the end of surgery did not block the increased aggregation.The patients undergoing angioplasty also showed a significant rise in the response to AA (5 mM), from 5.6 ± 5.5% pre-angioplasty to 32.4 ± 24.9% at the end of the procedure (p <0.0001), which fell significantly to 11.0 ± 8.1% 4 hours later. The antiplatelet activity of aspirin, mediated by blockade of platelet arachidonic acid metabolism, diminished significantly during surgery, but was partially restored by the end of the procedure without additional aspirin treatment.This rapidly inducible and transient effect may explain why some patients undergoing cardiovascular surgery remain at risk of peri-operative stroke and myocardial infarction.


2021 ◽  
Vol 10 (1) ◽  
pp. 33-38
Author(s):  
Rajeev Raj Manandhar ◽  
Krishna Raj Khanal ◽  
Himal Khanal ◽  
Saroj Gautam

Background: The pain and limitation of shoulder function can disrupt daily activities of patients for months to years. Adhesive capsulitis is considered a self-limiting disease but the duration remains uncertain. The brunt of the disease is focussed on the inflamed joint capsule. On this basis, use of corticosteroid injection is justified. However, injection method is not conclusive. Objectives: To compare clinical benefits of intra-articular injection alone versus combined intra-articular and subacromial injections in management of adhesive capsulitis. Methods: Fifty-nine patients with diagnostic criteria for adhesive capsulitis were included in the study from March 2019 to September 2020. Patients were divided into two groups; patients who underwent intra-articular (IA) injection alone (Group 1) and those who received both intra-articular and sub-acromial (IA+SA) injection (Group 2). The injections were landmark guided. Patients were followed up at three, six, and 12 weeks. Pain was recorded using visual analogue scale (VAS) and subjective function using Constant-Murley score. Results: Twenty-eight patients were included in Group 1 (IA) and 31 in Group 2 (IA+SA). Thirty-six patients were female (18 each in Group 1 and Group 2) and 23 patients were male (Group 1 = 13; Group 2 = 10). In the twelfth week, VAS score was reduced in both the groups. On comparing the mean value of Constant-Murley score between the two groups there is significant difference in value recorded at the sixth and twelfth week. Conclusion: The IA+SA injection provides significant reduction in pain and better function in the short term over the IA injection.


2019 ◽  
Vol 8 (9) ◽  
pp. 1486 ◽  
Author(s):  
Barbara De Angelis ◽  
Margarida Fernandes Lopes Morais D’Autilio ◽  
Fabrizio Orlandi ◽  
Giampiero Pepe ◽  
Simone Garcovich ◽  
...  

Chronic ulcers are characterized by loss of substance without a normal tendency towards spontaneous healing. The Wound Bed Preparation Guideline advises that after diagnosis, the expert should correct the biological state of the ulcer micro-environment based on TIME principles (Tissue, Infection, Moisture balance, Epidermal). There are many ways to treat such ulcers, for example through use of advanced dressings, negative pressure, surgical toilets, dermal substitutes, autologous skin grafting, and free or local flaps. In vitro and in vivo pre-clinical models hold widely acknowledged potential yet complex limitations. Tissue bioengineering could be an ideal approach to foster innovative strategies in wound healing. Our observational study reports on an in vitro and in vivo evaluation of a bio-functionalized scaffold composed of platelet-rich plasma (PRP) and hyaluronic acid (HA) used in 182 patients affected by chronic ulcers (diabetic and vascular), comparing the results with a control group of 182 patients treated with traditional dressings (HA alone). After 30 days the patients who had undergone the combined treatment (PRP + HA), showed 96.8% ± 1.5% re-epithelialization, as compared to 78.4% ± 4.4% in the control group (HA only). Within 80 days, they had 98.4% ± 1.3% re-epithelialization as compared to 87.8% ± 4.1% in the control group (HA only; p < 0.05). No local recurrence was observed during the follow-up period. PRP + HA treatment showed stronger regenerative potential in terms of epidermal proliferation and dermal renewal compared with HA alone.


2020 ◽  
Vol 48 (12) ◽  
pp. 030006052097603
Author(s):  
Aung Chan Thu ◽  
Sang Gyu Kwak ◽  
Win Nyi Shein ◽  
La Min Htun ◽  
Thae Thae Han Htwe ◽  
...  

Objective We evaluated the effect of ultrasound (US)-guided injection of platelet-rich plasma (PRP) into the shoulder joint in patients with adhesive capsulitis (AC) and compared its effect with that of conventional physiotherapy (CPT). Methods Sixty-four subjects with AC were included and randomly allocated into two groups, as follows: PRP (n=32; intra-articular [IA] PRP [4 mL] was injected); and CPT (n=32; short wave diathermy and exercise therapy were performed at three sessions/week for 6 weeks). Treatment outcomes evaluated therapeutic effectiveness before and at 1, 3, and 6 weeks after PRP injection and CPT initiation. Results Subjects in both groups showed a significant decrease in the visual analogue scale score for pain and shoulder and hand scores, and they a significant increase in shoulder passive range of motion at all evaluation time points. There was no significant difference in the measured outcomes between the two groups. However, there was less acetaminophen consumption after IA PRP injection compared with that after CPT. Conclusions IA PRP injection is a useful option for treating patients with AC, particularly those who have low therapeutic compliance for exercise therapy or have contraindications for corticosteroid injection or oral pain reduction medication.


2020 ◽  
Vol 10 (2) ◽  
pp. 182-188
Author(s):  
Kun Gui ◽  
Yu Huang ◽  
Meijin Wang ◽  
Jun Yang

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia, resulting in chronic respiratoryfailure and eventually death. β-catenin/Foxo1 showed a protective property in kidney fibrosis, but the role of β-catenin/Foxo1 in IPF was unclear. Our study aimed to investigate the role of β-catenin/Foxo1 in IPF and explore its underlying mechanism. The IPF model was established by injection of bleomycin (BLM) in vivo and stimulation by TGF-β1 in MRC5 cell in vitro. Haematoxylin-eosin staining and Masson’s trichrome staining were performed to examine histopathological injury in lung. Protein expression of corresponding genes was detected using western blot. Immunofluorescence staining assay was carried out to detect the expression of β-catenin, Foxo1, TCF and α-SMA. The expression levels of inflammatory cytokines were determined using ELISA kit assay. The results showed that BLM induced a serious pulmonary injury and proliferated fibroblasts. A higher interaction of β-catenin with TCF and a lower interaction of β-catenin with Foxo1 was found in BLM group compared to the control group. TGF-β1 promoted β-catenin/TCF, whereas ICG-001 inhibited β-catenin/TCF, and promoted β-catenin/Foxo1. Furthermore, ICG-001 reversed TGF-β1 induced largely production of inflammatory cytokines and accumulation of extracellular matrix, as well as high expression of α-SMA. However, AS1842856, a FOXO1 antagonist, strengthened the effects induced by TGF-β1. In summary, our study revealed that β-catenin/Foxo1 protected against IPF through inhibiting inflammatory response and extracellular matrix accumulation, providing an alternative approach to explain the potential mechanism of IPF and seek for more effective therapeutic drugs.


2019 ◽  
Vol 47 (13) ◽  
pp. 3238-3246 ◽  
Author(s):  
Joost C. Peerbooms ◽  
Paul Lodder ◽  
Brenda L. den Oudsten ◽  
Kamiel Doorgeest ◽  
Hans M. Schuller ◽  
...  

Background: When nonoperative treatment for chronic plantar fasciitis fails, often a corticosteroid injection is given. Corticosteroid injection gives temporary pain reduction but no healing. Platelet-rich plasma (PRP) has proven to be a safe therapeutic option in the treatment of tendon, muscle, bone, and cartilage injuries. Purpose: To determine the effectiveness of PRP as compared with corticosteroid injections for chronic plantar fasciitis. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Patients with chronic plantar fasciitis were allocated to have steroid injection or PRP. The primary outcome measure was the Foot Function Index (FFI) Pain score. Secondary outcome measures were function, as scored by the FFI Activity, FFI Disability, and American Orthopaedic Foot & Ankle Society, and quality of life, as scored with the short version of the World Health Organization Quality of Life (WHOQOL-BREF). All outcomes were measured at baseline and at 4, 12, and 26 weeks and 1 year after the procedure. Results: Of the 115 patients, 63 were allocated to the PRP group, of which 46 (73%) completed the study, and 52 were allocated to the control group (corticosteroid injection), of which 36 (69%) completed the study. In the control group, FFI Pain scores decreased quickly and then remained stable during follow-up. In the PRP group, FFI Pain reduction was more modest but reached a lower point after 12 months than the control group. After adjusting for baseline differences, the PRP group showed significantly lower pain scores at the 1-year follow-up than the control group (mean difference, 14.4; 95% CI, 3.2-25.6). The number of patients with at least 25% improvement (FFI Pain score) between baseline and 12-month follow-up differed significantly between the groups. Of the 46 patients in the PRP group, 39 (84.4%) improved at least 25%, while only 20 (55.6%) of the 36 in the control group showed such an improvement ( P = .003). The PRP group showed significantly lower FFI Disability scores than the control group (mean difference, 12.0; 95% CI, 2.3-21.6). Conclusion: Treatment of patients with chronic plantar fasciitis with PRP seems to reduce pain and increase function more as compared with the effect of corticosteroid injection. Registration: NCT00758641 (ClinicalTrials.gov identifier).


Author(s):  
Dwikora Novembri Utomo ◽  
I Gde Adi Widiastana

The addition of platelet rich plasma to mesenchymal stem cell culture on growth  media and  chondrogenic  media  had  any effect  on stem cell’s proliferation and differentiation into chondroblast has not been determined. This research is to find  out  the  effect  of  platelet  rich  plasma  on  mesenchymal  stem  cell’s differentiation and proliferation into chondroblast on in vitro media. Randomized control group posttest only design. Blood was taken from the rabbit’s vein to be processed into platelet rich plasma (PRP). Mesenchymal Stem Cell (MSC) was harvested from the bone marrow of the rabbit to be cultured. The MSC’s culture were divided into three groups of modification. The first group was combination of MSC added with Complete Culture Medium (CCM) and Chondrogenic Diferentation Medium (CDM) without PRP as control group. The second group had the same combination as the first group with extra 5% PRP. The third group had the same combination as the first group with extra 10% PRP. The results were evaluated in the following 21 days. The group that received extra 5% PRP had significant increase of chondroblast count compared to the group without PRP addition (p=0,033). The same result also occured on the groups that received extra 10% PRP compared to the group without PRP addition (p=0,028). There were no significant diferences between both the second and the third groupchondroblast count (p=0,203). There was a significant effect of platelet rich plasma on mesenchymal stem cell’s diferentiation and proliferation into chondroblast on invitro media.


Author(s):  
Dwikora Novembri Utomo ◽  
Anthoni Yusbida

Cartilage repair is a challenging clinical problem because the damage is an irreversible condition. Many studies had been performed using several kinds of natural or synthetic scaffold. Attempts to repair articular cartilage using scaffold usually found many problems, lacks the physical structure and mechanical properties necessary to ensure long-term efficacy to cartilage defect. Furthermore, scaffold frequently cause toxicity to the host. Therefore, this study was performed in vitro to test the toxicity effect of scaffold freeze dried bovine cartilage powder and platelets Rich Plasma (PRP). This research was conducted using pure experimental research design in 4 groups of animal stem cells which being added with scaffold freeze dried bovine cartilage scaffold provided with platelet rich plasma. This study using posttest only control group design. The result being processed with MTT assay and spectrophotometer for counting the viable stem cells. There was no significant difference in the amount of macrophage between control and the freeze dried bovine cartilage scaffold provided with PRP (p=0,128). With this result in the number of macrophages between the control with freeze dried bovine cartilage scaffold provided PRP, it can be concluded that these biomaterials have biocompatibility.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 9-9
Author(s):  
Mo Yang ◽  
Liang Li ◽  
Lixia Zhou ◽  
Hua Zhang ◽  
Liuming Yang ◽  
...  

Background: Platelets are produced by megakaryocytes and are primarily regulated by thrombopoietin (TPO). In the conditions of inflammation or stress, increased 5-HT and other inflammatory cytokines may affect liver and bone marrow to increase TPO and platelet production (Yang et al., Stem Cells, 2007; 2014). Mature megakaryocytes are fragmented in pulmonary circulation to generate more platelet intermediate proplatelets, then entered the circulation. We hypothesized that in patients with cerebral infarction, the secretion of inflammatory cytokines increases under stress or inflammatory conditions, increasing circulating TPO levels, followed by an increase in platelet production, and an increase in the number of platelet intermediate proplatelets. At the same time, platelets also have varying degrees of activation. Therefore, the increase in the number of proplatelets in the circulation and the increase in TPO levels may be the new pathological mechanism of cerebral infarction. Methods: The plasma levels of TPO were detected by ELISA. The in vivo proplatelets from patients were stained with CD41-FITC, which was further confirmed under a fluorescence microscope and flow cytometry. The in vitro proplatelets were observed in a culture system by CD41-FITC staining under a fluorescence microscope and flow cytometry detection. Results: Our clinical data demonstrated that patients with acute inflammation states, plasma TPO levels were significantly higher compared with healthy subjects (181.1 ± 35.38 vs 96.1 ± 9.7 pg/ml, p&lt;0.001, n=65), which may act as an acute response protein to protect the body. We also detected 20 patients with cerebral infarction and 20 normal controls and found that the plasma TPO levels of cerebral infarction patients (186.2±12.5 pg/ml) was significantly higher than that of the control group (122.3±10.2 pg/ml). The number of platelets in patients with cerebral infarction (222.11±8.55 ×109/L, n=20) was slightly higher than that in the control group (206.55±8.83 ×109/L, n=20). More importantly, we found more large platelets or proplatelets in the circulating blood of patients with cerebral infarction, which was significantly different from the control group (n=8). Furthermore, in vitro study confirmed that in 200 megakaryocytes (MKs), (18±2.5)% of MKs producing proplatelets in the TPO group (100 ng/ml), and in 5-HT group (100 nM), (15±3.2)% of MKs producing proplatelets, while the control group was only (7±3.2)% (n=5). At the same time, the effects of TPO and 5-HT were interfered by the corresponding receptor blockers, confirming that their effects were mediated by its receptors. The study further confirmed that both TPO and 5-HT affect the cytoskeleton by activating p-ERK1/2, reorganizing F-actin to generate proplatelets, and its role was blocked by PD98059. Conclusions: The study demonstrated that increased numbers of proplatelets in circulation and elevated plasma TPO levels may be novel pathological mechanisms of cerebral infarction Disclosures No relevant conflicts of interest to declare.


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