The Banff Patellar Instability Instrument: validity and reliability of an Indonesian version.

BACKGROUND: The Banff Patellar Instability Instrument (BPII) is a valuable scoring tool for assessing patellofemoral instability in patients suffering from patellofemoral pain syndrome (PFPS). The BPII 2.0 is a shortened version of the BPII. However, there is no Indonesian edition of BPII 2.0 that has been validated. This study aimed to determine the validity and reliability of the Indonesian version of the BPII 2.0. MATERIALS AND METHODS: This was a cross-sectional study that used a forward-backward translation protocol to create an Indonesian version of the BPII 2.0. Thirty patients with PFPS were given the questionnaires. The questionnaire's validity was evaluated by analyzing the correlation between score of each subscale and the overall score to the Indonesian version of the Kujala score using Pearson correlation coefficient, while the reliability was evaluated by measuring the internal consistency (Cronbach α) and test-retest reliability (intraclass correlation coefficient). RESULTS: The Indonesian version of BPII 2.0 and the Indonesian version of Kujala score had a strong Pearson correlation coefficient for construct validity. For all subscales, Cronbach α was 0.90-0.98, indicating adequate internal consistency. The test-retest reliability was high, with intraclass correlation coefficient ranging from 0.89 to 0.98 for all subscales. There was no difference in the Indonesian version of BPII 2.0 response between the first and second administration of the questionnaire which was taken 7 days afterward. CONCLUSION: The Indonesian version of BPII 2.0 was determined to be valid and reliable and is therefore an objective instrument to evaluate patellofemoral instability in patients with PFPS in the Indonesian population.

Mismatched knee implants in Indonesian and Dutch patients: a need for increasing the size.

PURPOSE: The aim of this study was to evaluate the anthropometric differences between knees of Indonesian Asians and Dutch Caucasians and the fit of nine different knee implant systems. METHODS: A total of 268 anteroposterior (AP) and lateral knee preoperative radiographs from 134 consecutive patients scheduled for total knee arthroplasty at two different centres in Jakarta and Leiden were included. Both patient groups were matched according to age and sex and included 67 Asians and 67 Caucasians. We assessed the radiographic differences between the Asian and Caucasian anthropometric data. The dimensions of the nine knee implant designs (Vanguard, Genesis II, Persona Standard, Persona Narrow, GK Sphere, Gemini, Attune Standard, Attune Narrow, and Sigma PFC) were compared with the patients' anthropometric (distal femur and proximal tibia) measurements. RESULTS: The Dutch Caucasian patients had larger mediolateral (ML) and AP femoral and tibial dimensions than the Indonesian Asians. The aspect ratios of the distal femur and tibia were larger in Asians than in Caucasians. The AP and ML dimensions were mismatched between the tibial components of the nine knee systems and the Asian anthropometric data. Both groups had larger ML distal femoral dimensions than the knee systems. CONCLUSION: Absolute and relative differences in knee dimensions exist not only between Asian and Caucasian knees but also within both groups. Not all TKA systems had a good fit with the Asian and Caucasian knee phenotypes. An increase in the range of available knee component sizes would be beneficial, although TKA remains an adequate compromise. LEVEL OF EVIDENCE: III.

Does Circumferential Patellar Denervation Result in Decreased Knee Pain and Improved Patient-reported Outcomes in Patients Undergoing Nonresurfaced, Simultaneous Bilateral TKA?

BACKGROUND: Anterior knee pain, which has a prevalence of 4% to 49% after TKA, may be a cause of patient dissatisfaction after TKA. To limit the occurrence of anterior knee pain, patellar denervation with electrocautery has been proposed. However, studies have disagreed as to the efficacy of this procedure.Questions/purposes We evaluated patients undergoing bilateral, simultaneous TKA procedures without patellar resurfacing to ask: (1) Does circumferential patellar cauterization decrease anterior knee pain (Kujala score) postoperatively compared with non-cauterization of the patella? (2) Does circumferential patellar cauterization result in better functional outcomes based on patient report (VAS score, Oxford knee score, and Knee Injury and Osteoarthritis Outcome Score) than non-cauterization of the patella? (3) Is there any difference in the complication rate (infection, patellar maltracking, fracture, venous thromboembolism, or reoperation rate) between cauterized patellae and non-cauterized patellae? METHODS: Seventy-eight patients (156 knees) were included in this prospective, quasi-randomized study, with each patient serving as his or her own control. Patellar cauterization was always performed on the right knee during simultaneous, bilateral TKA. Five patients (6%) were lost to follow-up before the 2-year minimum follow-up interval. A single surgeon performed all TKAs using the same type of implant, and osteophyte excision was performed in all patellae, which were left unresurfaced. Patellar cauterization was performed at 2 mm to 3 mm deep and approximately 5 mm circumferentially away from the patellar rim. The preoperative femorotibial angle and degree of osteoarthritis (according to the Kellgren-Lawrence grading system) were measured. Restoration of the patellofemoral joint was assessed using the anterior condylar ratio. Clinical outcomes, consisting of clinician-reported outcomes (ROM and Kujala score) and patient-reported outcomes (VAS pain score, Oxford knee score, and Knee Injury and Osteoarthritis Outcome Score), were evaluated preoperatively and at 1 month and 2 years postoperatively. Preoperatively, the radiologic severity of osteoarthritis, based on the Kellgren-Lawrence classification, was not different between the two groups, nor were the baseline pain and knee scores. The mean femorotibial angle of the two groups was also comparable: 189° ± 4.9° and 191° ± 6.3° preoperatively (p = 0.051) and 177° ± 2.9° and 178° ± 2.1° postoperatively (p = 0.751) for cauterized and non-cauterized knees, respectively. The preoperative (0.3 ± 0.06 versus 0.3 ± 0.07; p = 0.744) and postoperative (0.3 ± 0.06 versus 0.2 ± 0.07; p = 0.192) anterior condylar ratios were also not different between the cauterized and non-cauterized groups. RESULTS: At the 2-year follow-up interval, no difference was observed in the mean Kujala score (82 ± 2.9 and 83 ± 2.6 for cauterized and non-cauterized knees, respectively; mean difference 0.3; 95% confidence interval, -0.599 to 1.202; p = 0.509). The mean VAS pain score was 3 ± 0.9 in the cauterized knee and 3 ± 0.7 in the non-cauterized knee (p = 0.920). The mean ROM was 123° ± 10.8° in the cauterized knee and 123° ± 10.2° in the non-cauterized knee (p = 0.783). There was no difference between cauterized and non-cauterized patellae in the mean Knee Injury and Osteoarthritis Outcome Score for symptoms (86 ± 4.5 versus 86 ± 3.9; p = 0.884), pain (86 ± 3.8 versus 86 ± 3.6; p = 0.905), activities (83 ± 3.2 versus 83 ± 2.8; p = 0.967), sports (42 ± 11.3 versus 43 ± 11.4; p = 0.942), and quality of life (83 ± 4.9 versus 83 ± 4.7; p = 0.916), as well as in the Oxford knee score (40 ± 2.1 versus 41 ± 1.9; p = 0.771). Complications were uncommon and there were no differences between the groups (one deep venous thromboembolism in the cauterized group and two in the control group; odds ratio 0.49, 95% CI, 0.04-5.56; p = 0.57). CONCLUSIONS: Patellar cauterization results in no difference in anterior knee pain, functional outcomes, and complication rates compared with non-cauterization of the patella in patients who undergo non-resurfaced, simultaneous, bilateral, primary TKA with a minimum of 2 years of follow-up. We do not recommend circumferential patellar cauterization in non-resurfaced patellae in patients who undergo TKA. LEVEL OF EVIDENCE: Level II, therapeutic study.

Mechanism of spinal cord injury regeneration and the effect of human neural stem cells-secretome treatment in rat model.

BACKGROUND: Globally, complete neurological recovery of spinal cord injury (SCI) is still less than 1%, and 90% experience permanent disability. The key issue is that a pharmacological neuroprotective-neuroregenerative agent and SCI regeneration mechanism have not been found. The secretomes of stem cell are an emerging neurotrophic agent, but the effect of human neural stem cells (HNSCs) secretome on SCI is still unclear. AIM: To investigate the regeneration mechanism of SCI and neuroprotective-neuroregenerative effects of HNSCs-secretome on subacute SCI post-laminectomy in rats. METHODS: An experimental study was conducted with 45 Rattus norvegicus, divided into 15 normal, 15 control (10 mL physiologic saline), and 15 treatment (30 µL HNSCs-secretome, intrathecal T10, three days post-traumatic). Locomotor function was evaluated weekly by blinded evaluators. Fifty-six days post-injury, specimens were collected, and spinal cord lesion, free radical oxidative stress (F2-Isoprostanes), nuclear factor-kappa B (NF-κB), matrix metallopeptidase 9 (MMP9), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), transforming growth factor-beta (TGF-ß), vascular endothelial growth factor (VEGF), B cell lymphoma-2 (Bcl-2), nestin, brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) were analyzed. The SCI regeneration mechanism was analyzed using partial least squares structural equation modeling (PLS SEM). RESULTS: HNSCs-secretome significantly improved locomotor recovery according to Basso, Beattie, Bresnahan (BBB) scores and increased neurogenesis (nestin, BDNF, and GDNF), neuroangiogenesis (VEGF), anti-apoptotic (Bcl-2), anti-inflammatory (IL-10 and TGF-ß), but decreased pro-inflammatory (NF-κB, MMP9, TNF-α), F2-Isoprostanes, and spinal cord lesion size. The SCI regeneration mechanism is valid by analyzed outer model, inner model, and hypothesis testing in PLS SEM, started with pro-inflammation followed by anti-inflammation, anti-apoptotic, neuroangiogenesis, neurogenesis, and locomotor function. CONCLUSION: HNSCs-secretome as a potential neuroprotective-neuroregenerative agent for the treatment of SCI and uncover the SCI regeneration mechanism.

The Role of Human Neural Stem Cell Secretomes on the Repair of Spinal Cord Injury Post-laminectomy in Rattus norvegicus Through the Analysis of Basso-Beattie-Bresnahan Score Locomotors, Interleukin-10, Matrix Metalloproteinase 9, and Transforming Growth Factor-ß.

STUDY DESIGN: Experimental animal study. PURPOSE: This study aims to investigate the effects of treatment with human neural stem cell (HNSC) secretomes on subacute spinal cord injury (SCI) post-laminectomy by analyzing interleukin-10 (IL-10), matrix metalloproteinase 9 (MMP9), transforming growth factor-ß (TGF-ß), and Basso-Beattie-Bresnahan (BBB) score locomotors as expressions of neurological recovery. OVERVIEW OF LITERATURE: In the United States, SCI has a recovery rate of 0.08%, tetraplegia 58.7%, and paraplegia 40.6%. Therapeutic approaches to SCI have focused on modulating the secondary cascade to prevent neurological deterioration and glial scar formation. Increasing evidence has shown that the success of cell-based SCI therapy is attributed to the secretomes rather than the cells themselves, but the effect of treatment with HNSC secretomes in SCI is unclear. METHODS: This experimental study investigated 15 Rattus norvegicus rats that were divided into three groups: (1) normal, (2) SCI+nonsecretome, and (3) SCI+secretome (30 µL, intrathecal Th10). Model subacute SCI post-laminectomy was performed in 60 seconds using an aneurysm Yasargil clip with a closing forceps weighing 65 g (150 kdyn). At 35 days post-injury, the specimens were collected, and the immunohistochemicals of IL-10, MMP9, and TGF-ß were analyzed. Motor recovery was evaluated based on the BBB scores. RESULTS: The SCI post-laminectomy of rats treated with HNSC secretomes showed improvements in their locomotor recovery based on the BBB scores (p =0.000, mean=18.4) and decreased MMP9 (p =0.015) but had increased the levels of IL-10 (p =0.045) and TGF-ß (p =0.01). CONCLUSIONS: These results indicate that the factors associated with the HNSC secretomes can mitigate their pathophysiological processes of secondary damage after SCI and improve the locomotor functional outcomes in rats.

The mechanism of human neural stem cell secretomes improves neuropathic pain and locomotor function in spinal cord injury rat models: through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities.

Background: Globally, spinal cord injury (SCI) results in a big burden, including 90% suffering permanent disability, and 60%-69% experiencing neuropathic pain. The main causes are oxidative stress, inflammation, and degeneration. The efficacy of the stem cell secretome is promising, but the role of human neural stem cell (HNSC)-secretome in neuropathic pain is unclear. This study evaluated how the mechanism of HNSC-secretome improves neuropathic pain and locomotor function in SCI rat models through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities. Methods: A proper experimental study investigated 15 Rattus norvegicus divided into normal, control, and treatment groups (30 µL HNSC-secretome, intrathecal in the level of T10, three days post-traumatic SCI). Twenty-eight days post-injury, specimens were collected, and matrix metalloproteinase (MMP)-9, F2-Isoprostanes, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-ß, and brain derived neurotrophic factor (BDNF) were analyzed. Locomotor recovery was evaluated via Basso, Beattie, and Bresnahan scores. Neuropathic pain was evaluated using the Rat Grimace Scale. Results: The HNSC-secretome could improve locomotor recovery and neuropathic pain, decrease F2-Isoprostane (antioxidant), decrease MMP-9 and TNF-α (anti-inflammatory), as well as modulate TGF-ß and BDNF (neurotrophic factor). Moreover, HNSC-secretomes maintain the extracellular matrix of SCI by reducing the matrix degradation effect of MMP-9 and increasing the collagen formation effect of TGF-ß as a resistor of glial scar formation. Conclusions: The present study demonstrated the mechanism of HNSC-secretome in improving neuropathic pain and locomotor function in SCI through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities.

Double membrane platelet-rich fibrin (PRF) - Synovium succeeds in regenerating cartilage defect at the knee: An experimental study on rabbit.

Background: This study aims to prove the healing results (regeneration) in cartilage defects using a combination treatment of microfractures and transplantation synovium-platelet rich fibrin (S-PRF). Methods: A cartilage defect was made in the trochlear groove of the knee of adult New Zealand white rabbits, and was classified into three treatment groups. The group 1 was cartilage defect without treatment, 2 with microfracture treatment, and 3 with microfracture covered with a synovium-platelet rich fibrin (S-PRF) membrane. Twelve weeks after the intervention, the animals were macroscopically and histologically examined, and evaluated by the International Cartilage Repair Society (ICRS). Additionally, the expression of aggrecan and type 2 collagen was examined by real-time-PCR. Results: The ICSR scores for macroscopic were significantly higher in the microfracture and S-PRF transplant group than in the other groups. Also, the ICSR scores for histology were significantly higher in this group. The expression of aggrecan and type 2 collagen was higher in the group that received complete treatment. Conclusions: Microfractures and transplantation of synovium-platelet rich fibrin (S-PRF) can regenerate knee cartilage defects which have been shown to increase the expression of mRNA aggrecan and mRNA type 2 collagen resulting in excellent repair.

The effect of preconditioning hypoxia in schwann-like-cells-derived adipose mesenchymal stem cells and rat sciatic nerve-derived stem cells: experimental research.

The preconditioning hypoxia for stem cells is a strategy to achieve effective conditions for cell therapy, indicate increased expression of regenerative genes in stem cell therapy, and enhance the secretion of bioactive factors and therapeutic potential of their cultured secretome. Objectives: This study aims to explore the response of Schwann-like cells derived from adipose-derived mesenchymal stem cells (SLCs) and Schwann cells rat sciatic nerve-derived stem cells (SCs) with their secretomes under normoxic and hypoxic conditions in vitro. Material and methods: SLCs and SCs were isolated from the adipose tissue and the sciatic nerve of the adult white male rat strain Wistar. Cells were incubated in 21% O2 (normoxic group) and 1%, 3%, and 5% O2 (hypoxic group) conditions. Concentration values of transforming growth factor-ß (TGF-ß), basic Fibroblast Growth factor (bFGF), brain-derived neurotrophic factor, glial-derived neurotrophic factor, vascular endothelial growth factor, and nerve growth factor were detected and calculated utilizing an enzyme-linked immunosorbent assay, and the growth curve was described. Results: SLCs and SCs indicated positive expression for mesenchymal markers and negative expression for hematopoietic markers. Normoxic conditions SLCs and SCs showed elongated and flattened morphology. Under hypoxic conditions, SLCs and SCs showed a classic fibroblast-like morphology. Hypoxia 1% gave the highest concentration in TGF-ß and bFGF from the SLCs group and TGF-ß, bFGF, brain-derived neurotrophic factor, and vascular endothelial growth factor from the SCs group. No significant differences in concentration of growth factors between the SLCs group compared to SCs group in all oxygen groups. Conclusions: Preconditioning hypoxia has an effect on the composing of SLCs, SCs, and their secretomes in vitro; no significant differences in concentration of growth factors between the SLCs group compared with the SCs group in all oxygen groups.

An update of current therapeutic approach for Intervertebral Disc Degeneration: A review article.

Intervertebral disc degeneration is a natural process of aging. It can cause physical, psychological, and socioeconomic impact due to the decreasing function of the spine and pain manifestation. Conservative and surgical treatment to correct symptoms and structural anomalies does not fully recover the degenerated disc. Several therapeutic approaches have been developed to improve the clinical result and patient's quality of life. This paper aims to review previous studies that discussed potential novel approach in order to make effective degenerated disc restoration. We tried to briefly describe IVD, IDD, also review several promising current therapeutic approaches for degenerated disc treatment, including its relevance to the degeneration process and limitation to be applied in a clinical setting. There are generally four current therapeutic approaches that we reviewed; growth factors, small molecules, gene therapy, and stem cells. These new approaches aim to not only correct the symptoms but also restore and delay the degeneration process.

Hypoxia Effects in Intervertebral Disc-Derived Stem Cells and Discus Secretomes: An in vitro Study.

Background: This study aimed to investigate the effects of hypoxia and normoxia preconditioning in rabbit intervertebral disc-derived stem cells (IVDSCs) and discus-derived conditioned medium (DD-CM)/secretomes in vitro. Transforming growth factor (TGF)-ß1, platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF) have a role in the proliferation, development, differentiation, and migration of MSCs. Materials and Methods: Intervertebral discs were isolated from rabbit and incubated in normoxia and hypoxia 1%, 3%, and 5% (hypoxia groups) condition. Cell counting was performed after 24 hours of manipulation, then analyzed using one-way ANOVA. TGF-ß1, PDGF, FGF, and VEGF were measured using the ELISA. Results: The highest number of cells was in the hypoxia 3% preconditioning compared to the normoxia, hypoxia 1%, and hypoxia 5% groups. Hypoxia 3% also had the highest increase in PDGF protein production compared to normoxia, with hypoxia 1% and 5%. Among hypoxia groups, the highest secretions of VEGF and FGF proteins were in the hypoxia 3% group. Based on TGF-ß1 protein measurement, the hypoxia 1% group was the highest increase in this protein compared to other groups. Conclusion: Oxygen level in hypoxia preconditioning has a role in the preparation of IVDSCs and secretome preparation in vitro. The highest cell numbers were found in the treatment group with 3% hypoxia, and 3% hypoxia was significantly related to support IVDSCs preparation. Preconditioning with 3% hypoxia had higher PDGF and VEGF levels than other hypoxia groups.

Effect of combined locomotor training and aerobic exercise on increasing handgrip strength in elderly with locomotive syndrome: A randomised controlled trial.

Background: Elderly with the locomotive syndrome is at high risk for fall and fractures. Thus multimodal therapy is needed to minimize the risk. Objective: Analyzing the effect of combined locomotor training and aerobic exercise on muscle strength in elderly with locomotive syndrome stage 1. Methods: This study used a pre-test and post-test design with 20 participants (treatment group = 10 participants and control group = 10 participants). The treatment group was given combined locomotor training and aerobic exercise, while the control group was only given aerobic exercise for eight weeks. Locomotor training was provided three times/week with progressive increase of set and repetition at each activity. Meanwhile, aerobic exercise was given seven times/week for 30 min per session. Participants were examined for muscle strength (handgrip strength) before and after the intervention. The analysis included paired t-test and an independent t-test with a p-value <0.05. Results: The participants' mean age was 73.85 ± 4.75 years, with treatment group = 75.4 ± 4.88 years and control group = 72.3 ± 4.30 years (t = 1.508; 95% CI = -1.220 - 7420; p = 0.149). The HGS values in the treatment group were 13.89 ± 5.27 (pre-test) and 19.06 ± 4.54 (post-test; t = 11.765; 95% CI = -6.164 to -4.176; p < 0.001). Meanwhile, the HGS values in the control group at pre-test and post-test were 11.27 ± 2.17 and 13.03 ± 2.54, respectively (t = 2.057; 95% CI = -1.600 - 0.076; p = 0.070). The ΔHGS values of treatment and control group were 5.17 ± 1.39 and 1.76 ± 2.07, respectively (t = 4.329; 95% CI = 1.755-5.065; p < 0.001). Conclusion: Combined locomotor training and aerobic exercise have increased muscle strength, as proven by increased handgrip strength.

Implant surface modifications as a prevention method for periprosthetic joint infection caused by Staphylococcus aureus: a systematic review and meta-analysis.

Background: Periprosthetic joint infection is the most common infection due to joint replacement. It has been reported that, over a 5-year time span, 3.7 % of cases occurred annually. This statistic has increased to 6.86 % over 16 years. Thus, an effective method is required to reduce these complications. Several strategies such as coating methods with various materials, such as antibiotics, silver, and iodine, have been reported. However, the best preventive strategy is still undetermined. Therefore, this systematic review aims to evaluate the outcome of coating methods on joint arthroplasty as a treatment or preventive management for infection complications. Methods: Eligible articles were systematically searched from multiple electronic databases (PubMed, Cochrane library, and ScienceDirect) up to 2 June 2022. Based on the criterion inclusion, eight articles were selected for this study. The Newcastle-Ottawa scale (NOS) was used to assess the quality of the study, and the meta-analysis test was conducted with Review Manager 5.4. Results: The quality of the articles in this study is in the range of moderate to good. It was found that the application of modified antibiotic coatings significantly reduced the occurrence of periprosthetic joint infection (PJI) ( p 0.03), and silver coating could not significantly ( p 0.47) prevent the occurrence of PJI. However, according to the whole aspect of coating modification, the use of antibiotics, silver, and iodine can minimize the occurrence of PJI ( p   < 0.0001 ). Conclusion: Coating methods using antibiotics are an effective method that could significantly prevent the occurrence of PJI. On the other hand, coating with non-antibiotic materials such as silver could not significantly prevent the incidence of PJI.

Periosteum-induced ossification effect in skull defect through interleukin-8 and NF-κB pathway: An experimental study with Oryctolagus cuniculus rabbits.

Background: The purpose of this study was to analyze the response of inflammatory cytokines interleukin-8 (IL-8) and NF-κB to the closure of skull defect with periosteum as a scaffolding material in bone healing used after surgery. Methods: Thirty Oryctolagus cuniculus rabbits underwent a craniotomy to create a 20 mm diameter round defect in the parietal bones. The parietal bones were returned to its place and stabilized by an internal plate fixation. The defects were either left empty or implanted with periosteum. At 6 weeks, the specimens were euthanized and examined. Results: Histological examination showed a more well-developed formation of woven bone in the periosteum group. Immunohistochemical examinations showed that the use of periosteum in the closure of skull defects reduced the NF-κB and IL-8 response which affected the ossification process. Conclusion: The experiment showed that the use of periosteum was linked with IL-8 and NF-κB downregulation toward ossification effects at any point throughout the trial. Periosteum usage might be beneficial as a scaffolding material in bone healing for autograft cranioplasty in animal model and could be applied to clinical practice.

Prospect of Stem Cells as Promising Therapy for Brachial Plexus Injury: A Systematic Review.

Background: Brachial plexus injury is an advanced and devastating neurological injury, for which both nerve surgery and tendon transfers sometimes remain insufficient in restoring normal movement. Stem cell therapy may be applicable to rescue the injured motor neurons from degeneration which potentially improves muscle strength. Study Design: Systematic Review; Level of evidence V. Data Sources: A systematic literature search was conducted on PubMed (MEDLINE), EMBASE, the Cochrane Library, and Scopus using the terms ("stem cell") AND ("brachial plexus") as search keywords. Methods: The process of study selection was summarized by PRISMA flow diagram. The study included in vivo and in vitro studies with English language, humans or animals with some brachial plexus injuries, interventions, some applications of stem cells to the groups of study, with functional, biomechanical, or safety outcomes. Results: In total, there were 199 studies identified from the literature sources where 75 articles were qualified for forward evaluation following selecting the titles and abstracts. Ten studies were finally included in this systematic review after full-text assessment. Stem cells can produce neurotrophic factors in vitro and in vivo in rats, and their level was increased after injury. Electrophysiological measurement showed that the intervention group had distinctly higher CMAP amplitude and evidently shorter CMAP latency than the model group. Application of bone marrow stem cells (BMSCs) showed an elevation in the numbers of axons and density of myelinated fibers, the density of nerve fibers, the diameter of regenerating axons, and a decrease in axonal degeneration. A study in humans indicated an improvement of the movements in a patient with traumatic total BPI after injection of Ad-MSC. It is associated with increased muscle mass and sensory recovery and also suggested that mononuclear cell injection enhances muscle regeneration and reinnervation in the partly denervated muscle of brachial plexus injury. Various muscle groups had obtained strength together with restoration, the muscle strength attained after the previous transplantation were preserved. The results of this review support stem cell treatment in brachial plexus injury. Conclusion: This review provides evidence of the positive effects of stem cell treatment in brachial plexus injury.

Adipose-Derived Stem Cells (ASCs) for Regeneration of Intervertebral Disc Degeneration: Review Article.

The intervertebral disc (IVD) is an important structure in the human body because it functions as a weight-bearing. This structure undergoes a process of degeneration like the rest of the body and this process is known as intervertebral disc degeneration (IDD) which is the most common cause of low back pain (LBP). The current common management, either conservative or surgical, is pain-relieving and has not been able to restore degenerated disc optimally. Changes in the IVD microenvironment in IDD conditions make it difficult for the regeneration process to occur. Research to reverse the degeneration process continues to develop, one of them is the use of adipose-derived stem cells (ASCs). ASCs is superior due to the ability to differentiate into several other cells such as adipocytes, chondrocytes, and osteoblasts, it also has ability to act as immunomodulators by stimulating the migration of immune cells to damaged tissues. ASCs becomes a good choice because it is easy to obtain, low donor site morbidity, high proliferation rate, and excellent differentiation abilities. Research on the optimal preparation process for ASCs and their application to various disorders continues to advanced. This study aims to review the potential use of ASCs for regeneration of intervertebral disc degeneration.

The Escalation of Osteosarcoma Stem Cells Apoptosis After the Co-Cultivation of Peripheral Blood Mononuclear Cells Sensitized with Mesenchymal Stem Cells Secretome and Colony Stimulating Factor-2 in vitro.

INTRODUCTION: Peripheral blood mononuclear cells (PBMCs) sensitized with mesenchymal stem cells (MSCs) secretome and/or colony stimulating factor-2 (CSF-2) as an immunotherapy candidate may escalate osteosarcoma stem cells (OS-SCs) apoptosis. This study aimed to investigate the escalation of osteosarcoma stem cells' apoptosis after the co-cultivation with PBMCs sensitized by MSCs secretome with/or CSF-2 and it was completed by analyzing the level of serum tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) and tumor necrosis factor-α (TNF-α) level, annexin V binding, caspase-3 and caspase-8 expression in vitro. METHODS: OS-SCs were derived from a single human osteosarcoma sample with its high grade and osteoblastic essential clinical characteristics obtained from a biopsy before the chemotherapy treatment. They were then isolated and cultured confirmed by the cluster of differentiation-133 (FITC) by applying immunofluorescence analysis with fluorescein isothiocyanate (FITC) labeled. MSCs secretome was obtained with cells extracted from the bone marrow of a healthy patient. Furthermore, enzyme linked immunosorbent assay (ELISA) was utilized to analyze sTRAIL and TNF-α level in each group. The expression of caspase-3, caspase-8, and annexin V assay in each group was examined by applying the immunofluorescence labeled with FITC. The comparison analysis between treatment groups and the control group was performed by utilizing the analysis of variance (ANOVA) and continued with Tukey Honest Significant Difference (HSD) (p<0.05). RESULTS: There was a significant difference in the upregulation of sTRAIL and TNF-α level indicated by the increased annexin V, caspase-3, and caspase-8 expression binding between groups (p<0.05). CONCLUSION: MSCs Secretome and CSF-2 could significantly increase the activity of PBMCs through the improvement of sTRAIL and TNF-α levels which could lead to the escalation of OS-SCs apoptosis through an enhanced expression of caspase 3, caspase 8 and annexin V binding in vitro.

Ligament/Tendon Culture under Hypoxic Conditions: A Systematic Review.

The hypoxic environment is a substantial factor in maintenance, proliferation, and differentiation of the cell cultures. Low oxygen is known as a potent chondrogenesis stimulus in stem cells that is important for clinical application and engineering of functional cartilage. Hypoxia can potentially induce angiogenesis process by secretion of cytokines. This systematic review goal is to discover the effect of hypoxic condition on tendon/ ligament culture and the best oxygen level of hypoxia for in vitro and in vivo studies. We included 21 articles. A comprehensive review of this database confirms that the hypoxic condition is a substantial factor in the maintenance, proliferation, and differentiation of ligament/tendon cultures. Cell proliferation in the severe hypoxic (oxygen concentration of 1%) group at 24 h postcultivation was considered significant, but cell proliferation was markedly inhibited in the severe hypoxic group after 48 h.

Role of adipose mesenchymal stem cells and secretome in peripheral nerve regeneration.

The use of stem cells is a breakthrough in medical biotechnology which brings regenerative therapy into a new era. Over the past several decades, stem cells had been widely used as regenerative therapy and Mesenchymal Stem Cells (MSCs) had emerged as a promising therapeutic option. Currently stem cells are effective therapeutic agents againts several diseases due to their tissue protective and repair mechanisms. This therapeutic effect is largely due to the biomolecular properties including secretomes. Injury to peripheral nerves has significant health and economic consequences, and no surgical procedure can completely restore sensory and motor function. Stem cell therapy in peripheral nerve injury is an important future intervention to achieve the best clinical outcome improvement. Adipose mesenchymal stem cells (AdMSCs) are multipotent mesenchymal stem cells which are similar to bone marrow-derived mesenchymal stem cells (BM-MSCs). The following review aims to provide an overview of the use of AdMSCs and their secretomes in regenerating peripheral nerves.