Growth Factor Concentrate (GFC) for the Management of Osteoarthritis of the Knee: A Systematic Review.

Introduction: The knee is the most commonly affected joint in osteoarthritis (OA), affecting millions of people worldwide. Knee OA significantly impacts the activities of daily living (ADL) along with affecting overall quality of life of patients (QoL), thereby leading to substantial socio-economic burden. Conservative therapies are prioritized, resorting to surgery only when needed. However, these traditional approaches have limitations. Regenerative medicine, involving the use of orthobiologics, including autologous peripheral blood-derived orthobiologics such as growth factor concentrate (GFC), has evolved and shown potential for managing knee OA. The primary goal of this review is to summarize the results of in vitro, preclinical and clinical studies involving GFC for the management of knee OA. Methods: Multiple databases (PubMed, Scopus, Google Scholar, Web of Science and Embase) were searched applying terms for the intervention 'GFC' and treatment 'knee OA' for the studies published in the English language to March 10, 2024. Results: Only three clinical studies met our pre-defined criteria and were included in this review. Conclusion: Intra-articular administration of GFC is safe and potentially efficacious to manage OA of the knee. More, adequately powered, multi-center, prospective, RCTs are warranted to demonstrate the long-term effectiveness of GFC in patients suffering from mild-to-moderate knee OA and to justify its routine clinical use. Further studies evaluating the efficacy of GFC compared to other orthobiologics are also required to allow physicians/surgeons to choose the optimal orthobiologic for the treatment of OA of the knee.

The Glanular-Frenular Collar (GFC) technique: Dual approach to hypospadias reconstruction.

INTRODUCTION: The Glanular-Frenular Collar (GFC) technique has evolved since it was first described in 2017. The technique involves reconstruction of the septum glandis, which has been overlooked in the history of hypospadias, and formation of the frenulum, creating the ventral wall of the glanular urethra without dissecting the glans, leaving room for the formation of the navicular fossa. MATERIAL AND METHODS: We present a case of distal hypospadias corrected with the GFC technique and demonstrate the important steps of the surgical technique. RESULTS: The aesthetic result corresponded to the normal anatomy of the glans and frenular triangle, and the functional result showed a free and wavy shape of urine that resembled the normal flow from the urethra. DISCUSSION: In the normal anatomy of the penis, the wings of the glans are separated ventrally by the septum glandis and the frenulum. The navicular-shaped glanular urethra and its vertical, elliptical opening are covered by the fibroelastic septum glandis, unlike the penile urethra, which is surrounded by the corpus spongiosum. CONCLUSION: Reconstruction of hypospadias should include the formation of a septum glandis, frenulum, and navicular fossa. The GFC technique demonstrates the importance of a dual surgical approach for glanular and penile urethra reconstruction.

Underlying pharmacological mechanisms of psilocin-induced broadband desynchronization and disconnection of EEG in rats.

Introduction: Psilocybin is one of the most extensively studied psychedelic drugs with a broad therapeutic potential. Despite the fact that its psychoactivity is mainly attributed to the agonism at 5-HT2A receptors, it has high binding affinity also to 5-HT2C and 5-HT1A receptors and indirectly modulates the dopaminergic system. Psilocybin and its active metabolite psilocin, as well as other serotonergic psychedelics, induce broadband desynchronization and disconnection in EEG in humans as well as in animals. The contribution of serotonergic and dopaminergic mechanisms underlying these changes is not clear. The present study thus aims to elucidate the pharmacological mechanisms underlying psilocin-induced broadband desynchronization and disconnection in an animal model. Methods: Selective antagonists of serotonin receptors (5-HT1A WAY100635, 5-HT2A MDL100907, 5-HT2C SB242084) and antipsychotics haloperidol, a D2 antagonist, and clozapine, a mixed D2 and 5-HT receptor antagonist, were used in order to clarify the underlying pharmacology. Results: Psilocin-induced broadband decrease in the mean absolute EEG power was normalized by all antagonists and antipsychotics used within the frequency range 1-25 Hz; however, decreases in 25-40 Hz were influenced only by clozapine. Psilocin-induced decrease in global functional connectivity and, specifically, fronto-temporal disconnection were reversed by the 5-HT2A antagonist while other drugs had no effect. Discussion: These findings suggest the involvement of all three serotonergic receptors studied as well as the role of dopaminergic mechanisms in power spectra/current density with only the 5-HT2A receptor being effective in both studied metrics. This opens an important discussion on the role of other than 5-HT2A-dependent mechanisms underlying the neurobiology of psychedelics.

Comparison of PEG precipitation and ultrafiltration treatment for serum macroprolactin in Chinese patients with hyperprolactinemia.

BACKGROUND: Macroprolactinemia is a common cause of hyperprolactinemia (HPRL), with an average worldwide incidence of 18.9 %. This study aimed to explore the feasibility of ultrafiltration (UF) and polyethylene glycol (PEG) precipitation for macroprolactin screening, as well as the incidence and clinical characteristics of Chinese patients with macroprolactinemia. METHODS: In this study, 94 patients with HPRL and 206 healthy individuals were included. Gel filtration chromatography (GFC), PEG precipitation, and UF were used to screen for macroprolactin, and chemiluminescence was used to determine the prolactin levels. RESULTS: The detected incidence of macroprolactinemia in the patients with HPRL was 7.45% (7/94, GFC) and 5.32% (5/94, PEG precipitation). Patients with macroprolactinemia usually present with atypical clinical symptoms, moderately increased prolactin levels, and negative or microadenoma-positive pituitary images. In addition, the recovery of monomeric prolactin by PEG precipitation and UF was significantly correlated to that of GFC (r PEG = 0.493, P < 0.001; r UF = 0.226, P = 0.014), with a higher correlation coefficient between PEG precipitation and GFC. Furthermore, PEG precipitation had a smaller variation (95% confidence interval [CI]: -35.77% to 18.34%) than UF in monomeric prolactin recovery and substantial diagnostic consistency with GFC (Cohen's kappa coefficient = 0.647). The proportion of monomeric prolactin in patients with HPRL did not change significantly between the two visits within one year (P > 0.05). CONCLUSION: The incidence of macroprolactinemia in Chinese patients with HPRL is low in the present study. Based on our analysis, we recommend that only patients who are clinically suspected of having macroprolactinemia should be screened using PEG precipitation.

Serial intraarticular injections of growth factor concentrate in knee osteoarthritis: A placebo controlled randomized study.

Objective: To evaluate and compare clinical efficacy and effect on specific serum biomarker with serial injections of growth factor concentrate (GFC) for knee osteoarthritis (KOA) in a randomized triple blinded placebo controlled interventional study. Methods: Final assessment was done on 58 patients. Patients with Kellgren-Lawrence grade II, III knee osteoarthritis were administered monthly intraarticular injections(3 injections) of GFC(n = 31) or saline(n = 27) and evaluated clinically with visual analogue scale(VAS) and Western Ontario and McMaster Universities Arthritis Index(WOMAC) at 3,6 and 12 months post therapy. Biochemical analysis was done with serum biomarker of cartilage degeneration, Collagen 2-1 (Coll2-1), estimated at baseline and at final follow up. Results: Both the groups exhibited statistically significant improvements (P < 0.05) in VAS at 3,6 and 12 months. WOMAC improvement reached statistical significance for GFC group at every evaluation (P < 0.001) but only at 12 months in NS group (P = 0.029). The improvements were clinically meaningful only in GFC group throughout follow up (Minimal clinically important differences >12% of baseline in WOMAC and >2 cm difference in mean for VAS). Intergroup comparison revealed GFC to be much better for both scores at every evaluation (95% CI of 0.2-1.5,[P = 0.008], 1.4-2.9,[P < 0.0001], and 2.7-4.2,[P < 0.0001] for VAS, 7.3-16.0 [P < 0.001], 11.6-21.9 [P < 0.001] and 18.1-31.1[P < 0.001] for WOMAC). Statistically significant decrease in serum Coll2-1 levels were observed for GFC group only. No serious complications were seen. Conclusion: Serial(three) monthly GFC injections result in clinically meaningful improvement of subjective pain and function outcome scores, sustaining up to 12 months in KOA grade II and III. GFC also lead to significant reduction in serum levels of cartilage degradation biomarker coll2-1.

Deep Learning Solution for Quantification of Fluorescence Particles on a Membrane.

The detection and quantification of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus particles in ambient waters using a membrane-based in-gel loop-mediated isothermal amplification (mgLAMP) method can play an important role in large-scale environmental surveillance for early warning of potential outbreaks. However, counting particles or cells in fluorescence microscopy is an expensive, time-consuming, and tedious task that only highly trained technicians and researchers can perform. Although such objects are generally easy to identify, manually annotating cells is occasionally prone to fatigue errors and arbitrariness due to the operator's interpretation of borderline cases. In this research, we proposed a method to detect and quantify multiscale and shape variant SARS-CoV-2 fluorescent cells generated using a portable (mgLAMP) system and captured using a smartphone camera. The proposed method is based on the YOLOv5 algorithm, which uses CSPnet as its backbone. CSPnet is a recently proposed convolutional neural network (CNN) that duplicates gradient information within the network using a combination of Dense nets and ResNet blocks, and bottleneck convolution layers to reduce computation while at the same time maintaining high accuracy. In addition, we apply the test time augmentation (TTA) algorithm in conjunction with YOLO's one-stage multihead detection heads to detect all cells of varying sizes and shapes. We evaluated the model using a private dataset provided by the Linde + Robinson Laboratory, California Institute of Technology, United States. The model achieved a mAP@0.5 score of 90.3 in the YOLOv5-s6.

Information transmission in regional energy stock markets.

Since markets are undergoing severe turbulent economic periods, this study investigates the information transmission of energy stock markets of five regions including North America, South America, Europe, Asia, and Pacific where we differentiated the regional energy markets based on their developing and developed state of economy. We employed time-frequency domain from Jan 1995 to May 2021 and found that energy stocks of developed regions are highly connected. The energy markets of North America, South America, and Europe are the net transmitters of spillovers, whereas the Asian and Pacific energy markets are the net receivers of spillovers. The results also reveal that the connectedness of regional energy markets is time and frequency dependent. Regional energy stocks were highly connected following the Asian financial crisis (AFC), global financial crisis (GFC), European debt crisis (EDC), shale oil revolution (SOR), and COVID-19 pandemic. Time-dependent results reveal that high spillovers formed during stress periods and frequency domain show the higher connectedness of regional energy stock markets in the short run followed by an extreme economic condition. These results have significant implications for policymakers, regulators, investors, and regional controlling bodies to adopt effective strategies during short run to avoid economic downturns and information distortions.

The 2008 global financial crisis and COVID-19 pandemic: How safe are the safe haven assets?

We compare the performance of safe-haven assets during the Global Financial Crisis (GFC) and COVID-19 pandemic. First, regarding the GFC, we find, intermediate (weak) safe haven evidence for US dollar, Swiss franc and T-bonds (Gold, Silver and T-bills). Second, with regard to COVID, we find gold is very risky in some settings, while silver has become extremely risky. Collectively, our findings suggest that the character of safe-haven assets has changed between the crises. Therefore, investors should exercise extreme care when investing in potential safe-haven assets during times of market stress.

Volatility impacts on the European banking sector: GFC and COVID-19.

This paper analyses the volatility transmission between European Global Systematically Important Banks (GSIBs) and implied stock market volatility. A Dynamic Conditional Correlation Generalized Autoregressive Conditional Heteroskedasticity model is applied to determine the dynamic correlation between returns of Europe's GSIBs and the world's most prominent measure of market "fear", the CBOE Volatility Index (VIX). The results identify a higher negative co-relationship between the VIX and GSIB returns during the COVID-19 period compared with the Global Financial Crisis (GFC), with one-day lagged changes in the VIX negatively Granger-causing bank returns. The asymmetric impact of changes in implied volatility is examined by quantile regressions, with the findings showing that in the lower quartile-where extreme negative bank returns are present-jumps in the VIX are highly significant. This effect is more pronounced during COVID-19 than during the GFC. Additional robustness analysis shows that these findings are consistent during the periods of the Swine Flu and Zika virus epidemics.

How new Fed corporate bond programs cushioned the Covid-19 recession.

In the financial crisis and recession induced by the Covid-19 pandemic, many investment-grade firms became unable to borrow from securities markets. In response, the Fed not only reopened its commercial paper funding facility but also announced it would purchase newly issued and seasoned corporate bonds rated as investment grade before the Covid pandemic. We assess the effectiveness of this program using long sample periods, spanning the Great Depression through the Great and Covid Recessions. Findings indicate that the announcement of corporate bond backstop facilities helped stop risk premia from rising further than they had by late-March 2020. In doing so, these backstop facilities limited the role of external finance premia in amplifying the macroeconomic impact of the Covid pandemic. Nevertheless, the corporate bond programs blend the roles of the Federal Reserve in conducting monetary policy via its balance sheet, acting as a lender of last resort, and pursuing credit policies.

Are safe haven assets really safe during the 2008 global financial crisis and COVID-19 pandemic?

This study evaluates the safe-haven role of twelve assets against the US stock market during the 2008 global financial crisis (GFC) and the COVID-19 pandemic. Our results show that silver and the Islamic stock index were safe havens during the 2008 GFC, and the Islamic stock index and Tether have been safe havens during COVID-19. We observe that the Islamic stock index and Tether have emerged as strong new safe havens. However, our supplementary analysis reveals that gold and Bitcoin still exhibit safe-haven behavior during severe market downturns. Overall, our findings suggest that safe-haven assets may vary over time.

GFc7 as a Smart Growth Nanofactor for ex vivo Expansion and Cryoprotection of Humans' Hematopoietic Stem Cells.

BACKGROUND: Nowadays, smart synthesized nanostructures have attracted wide attention in the field of stem cell nanotechnology due to their effect on different properties of stem cells. METHODS: GFc7 growth nanofactor was synthesized based on nanochelating technology as an iron-containing copper chelator nanocomplex. The effect of this nanocomplex on the expansion and differentiation of hematopoietic stem cells (HSCs) as well as its performance as a cryoprotectant was evaluated in the present study. RESULTS: The results showed that the absolute count of CD34+ and CD34+CD38- cells on days 4, 7, 10 and 13; the percentage of lactate dehydrogenase enzyme on the same days and CD34+CXCR4 population on day 10 were significantly increased when they were treated with GFc7 growth nanofactor in a fetal bovine serum (FBS)-free medium. This medium also led to delayed differentiation in HSCs. One noticeable result was that CD34+CD38- cells cultured in an FBS medium were immediately differentiated into CD34+CD38+ cells, while CD34+CD38- cells treated with GFc7 growth nanofactor in FBS medium did not show such an immediate significant differentiation. De-freezing GFc7-treated CD34+ cells, which were already frozen according to cord blood bank protocols, showed a higher percentage of cell viability and a larger number of colonies according to colony-forming cell assay as compared to control. CONCLUSION: It can be claimed that treating HSCs with GFc7 growth nanofactor leads to quality and quantity improvement of HSCs, both in terms of expansion in vitro and freezing and de-freezing processes.

Garcinielliptone FC: Selective anti-amastigote and immunomodulatory effects on macrophages infected by Leishmania amazonensis.

The present study was directed to the in vitro antileishmanial, cytotoxic and immunomodulatory effects of Garcinielliptone FC (GFC) against promastigote and macrophage-internalized amastigote forms of Leishmania amazonensis. GFC showed in vitro cytotoxicity against BALB/c peritoneal macrophages with CC50 of 74.90 µM. The hemolytic activity against sheep erythrocytes only demonstrated a decrease of 20.42% in cell viability at the highest tested concentration tested (1326.0 µM). GFC promoted in vitro growth inhibition of both promastigote and intracellular amastigotes with IC50 values of 14.06 and 1.91 µM, respectively, with 7.3-fold higher Selectivity Index (SI) for intracellular amastigotes (SI = 39.21) than for promastigotes (SI = 5.33). Interestingly, the pre-treatment of macrophages or promastigotes with GFC promoted decrease of infected macrophages and number of recovered amastigotes, respectively. Also, GFC was able to markedly promote macrophages activation by increase of phagocytic capability and nitrite production at concentrations able to solve infection of macrophages by L. amazonensis, suggesting the possible involvement of immunomodulatory modulation of macrophages leading to solve the infection. GFC is an emerging and promising chemical compound for the studies focused on the assessment of its therapeutic potential on in vivo experimental models of leishmaniasis.

[Quantitative determination of the beta-2-microglobulin monomer by gel filtration chromatography].

Beta-2-microglobulin (B2M) is an important material in dialysis-related amyloidosis research. Unfortunately, the quantitative detection of the B2M monomer is difficult during B2M production. In this study, we established a method for the detection of the B2M monomer and its dimer in solution via gel filtration chromatography. The B2M powder was dissolved in 0.01 mol/L phosphate-buffered solution (PBS, pH 7.2-7.4) with a final mass concentration of 0.5 g/L. The B2M sample was analyzed on a TSKgel SuperSW2000 column (30 cm×4.6 mm, 4 µm) by an Agilent 1200 Series HPLC using 0.01 mol/L PBS (pH 7.2-7.4) as the mobile phase at a flow rate of 0.5 mL/min. The temperature of the column was 25℃, and the detection wavelength was 280 nm. The purities of the B2M monomer and the B2M dimer were tested. A series of concentrations of B2M monomer solutions were prepared to create a standard working curve. The standard working curve of the B2M monomer had a good linear relationship (coefficient of correlation (r2) was 0.9948). The limit of quantitation for the B2M monomer in PBS was 0.08 g/L (S/N=10). The recoveries were 85.0%-96.7% with relative standard deviations of 1.7%-3.3% at spiked levels of 0.10-0.30 g/L. The quantification of the B2M monomer was undisturbed by the B2M dimer, which can form during the B2M purification process. This determination method is simple, stable, and reliable for the determination of the B2M monomer in B2M industrial production.

Identification and characterization of flavor precursor peptide from beef enzymatic hydrolysate by Maillard reaction.

In this study, beef enzymatic hydrolysate was fractionated by sequential UF/GFC/RP-HPLC. RP-HPLC fractions were subjected to Maillard reaction with xylose. The FD/TD factors of the MRPs were prominent. Sensory evaluation showed that F-3 exhibited intense meaty taste; the kokumi intensity, umami-enhancing capacity in F-4; the umami-enhancing capacity in F-5; the umami intensity and umami-enhancing capacity in F-6. All these were strong in F-7 and F-8. The RP-HPLC fractions were subsequently analyzed by ESI-Q-TOF MS/MS. Of the 21 peptides identified, Leu(Ile)-X, Val-X, Phe-X, and Cys-containing peptides were the major ones. Six peptides (Leu-Cys, Glu-Cys-Gly, Cys-Gly-Val, Val-Met, Phe-Glu, and Phe-Gln) were synthesized and included in the Maillard reaction with xylose. FD factors of MRPs of all these synthesized peptides were significantly greater than those of fraction F-7. The stronger Maillard reactivity demonstrated by the synthesized peptides proves that this work is correct.

Lp8 is potentially associated with partial lecithin:cholesterol acyltransferase deficiency in a patient with primary biliary cirrhosis.

BACKGROUND: The significance of Lp8, that is, abnormal lipoprotein(s) detected in fraction 8 by combined high-performance liquid chromatography/gel filtration column in patients with familial lecithin:cholesterol acyltransferase (LCAT) syndrome, in relation to the severity of LCAT deficiency has not been analyzed. OBJECTIVE: We have studied Lp8 in a patient with primary biliary cirrhosis. METHODS: Plasma lipoproteins were analyzed using high-performance liquid chromatography/gel filtration column in the course of treatment of a 47-year-old female patient with primary biliary cirrhosis. RESULTS: Electrophoretic lipoprotein analyses showed massive accumulation of abnormal ß- and preß-lipoproteins with a minor lipoprotein fraction at a position near the cathode corresponding to Lp-X, on day A (status: hypercholesterolemia, LCAT activity undetectable). Chromatographic lipoprotein subfraction analysis revealed free cholesterol- and phospholipid-rich lipoproteins in fractions 1-6, corresponding to chylomicrons and very low-density lipoprotein, and phospholipid- and triglyceride-rich lipoproteins with increased free cholesterol, that is, Lp8, in fractions 7-9 (corresponding to low-density lipoprotein). On day B, after additional treatment for 7 months (status: almost normolipidemia, decreased LCAT activity), although the abnormal lipoprotein and the lipoproteins in fractions 1-6, were drastically decreased, the presence of Lp8 persisted. CONCLUSIONS: Lp8 likely is a minor abnormal lipoprotein fraction in patients with mildly decreased secondary LCAT activity, as well as with severely reduced primary LCAT activity.

An UPLC-MS/MS method for simultaneous determination of multiple constituents in Guizhi Fuling capsule with ultrafast positive/negative ionization switching.

Guizhi Fuling capsule (GFC), a traditional Chinese medicine (TCM) with effects of promoting blood circulation and dissipating blood stasis, has been widely used in the clinic. Because of the complex matrix and various chemical structure types, quality control of GFC remains great challenge. In the present study, an ultra performance liquid chromatography hybrid triple-quadrupole mass spectrometry (UPLC-QQQ MS) method with ultrafast positive/negative ionization switching was developed for simultaneous determination of 18 bioactive components in GFC, including methyl gallate, ethyl gallate, oxypaeoniflorin, benzoic acid, albiflorin, paeonolide, paeoniflorin, 1, 2, 3, 4, 6-pentagalloylglucose, mudanpioside C, benzoyloxypaeoniflorin, benzoylpaeoniflorin, pachymic acid, amygdalin, cinnamaldehyde, paeonol, cinnamic acid, 4-hydroxybenzoic acid, and gallic acid. Separation was performed on an Agilent Zorbax Extend-C18 column (2.1 mm × 50 mm, 1.8 µm), using a gradient elution with acetonitrile and water containing 0.1% formic acid. Cholic acid was selected as the internal standard. This newly developed method was fully validated for linearity, precision, accuracy, and stability, and then applied to quality assessment of GFC. Finally, the batch-to-batch reproducibility of GFC samples was evaluated by the cosine ration and Euclidean distance method, which showed high quality consistency. The results demonstrated that the developed method pro vided a reasonable and powerful manner for quality control of GFC.

An acid precipitation technique: A strip assay for the large-scale DNA polymerase activity screening.

A new format of a very rapid, low-cost and high-productive analysis based on the acid precipitation of radiolabeled DNA was developed. By contrast to the conventional processing of a large number of GF/C discs, the method employs one GF/C strip containing samples on individual teeth. The strip assay was validated by comparison with the glass fiber disk technique; the efficiency was demonstrated by screening E. coli superproducers and fractions obtained at the steps of Bst DNA polymerase, Large Fragment purification by the protocol we developed. The principle proposed allows simultaneous assaying many samples for the activity of different polymerases.

Simultaneous determination of seven bioactive components in Guizhi Fuling capsule by microwave-assisted extraction combined with ultra performance liquid chromatography tandem mass spectrometry.

A simple, rapid and reliable microwave-assisted extraction (MAE) combined with ultra performance liquid chromatography tandem mass spectrometry method was developed for simultaneous determination of the seven bioactive constituents in Guizhi Fuling capsule (GFC), namely gallic acid, amygdalin, albiflorin, paeoniflorin, paeonol, cinnamic acid and pachymic acid, respectively. The operation of MAE optimised through orthogonal array design experiment was performed at 80°C for 10 min with methanol-water (70:30, v/v) as the extracting solvent. The method was validated including intra- and inter-day precision, repeatability and stability, with relative standard deviation less than 3.9%, 3.3%, 4.4% and 3.1%, respectively. All analytes showed the good linearity (r >0.999), and their average recoveries varied between 98.2% and 101.2%. The results indicated that this method was simple, effective and suitable for the quality control of GFC.

Treatment of AVN Using Autologous BM Stem Cells and Activated Platelet-Derived Growth Factor Concentrates.

BACKGROUND: Avascular Necrosis (AVN) of hip is a devastating condition seen in younger individuals. It is the ischemic death of the constituents of the bone cartilage of the hip. The femoral head (FH) is the most common site for AVN. It results from interruption of the normal blood flow to the FH that fits into the hip socket. Earlier studies using autologous bone marrow stem cell concentrate injections have shown encouraging results with average success rates. The current study was designed to improve significantly the cartilage regeneration and clinical outcome. METHODS: Total of 48 patients underwent autologous bone marrow stem cell and activated platelet-rich plasma derived growth factor concentrate (PRP-GFC) therapy for early and advanced stages AVN of femoral head in a single multi-specialty center. The total treatment was divided into three phases. In the phase I, all the clinical diagnostic measurements such as magnetic resonance imaging (MRI), computed tomography (CT) etc. with respect to the AVN patients and bone marrow aspiration from posterior iliac spine from the patients were carried out. In the phase II, isolation of stem cells and preparation from the patients were performed. Subsequently, in phase III, the stem cells and PRP- GFCs were transplanted in the enrolled patients. RESULTS: Ninety three percent of the enrolled AVN patients showed marked enhancement in the hip bone joint space (more than 3mm) after combined stem cells and PRP-GFC treatment as evidenced by comparison of the pre- and post-treatment MRI data thus indicative of regeneration of cartilage. The treated patients showed significant improvement in their motor function, cartilage regrowth (3 to 10mm), and high satisfaction in the two-year follow-up. CONCLUSION: Combination of stem cell and PRP-GFC therapy has shown promising cartilage regeneration in 45 out of 48 patients of AVN. This study clearly demonstrates the safety and efficacy of this treatment. Larger numbers of patients need to be evaluated to better understand the efficacy of the combined stem cell and PRP-GFC therapy on AVN patients.