Autologous Bone Marrow-derived Stem Cells Research Articles

The use of autologous neurogenically-induced bone marrow-derived mesenchymal stem cells for the treatment of paraplegic dogs without nociception due to spinal trauma.

The aim of this study was to investigate the effects of percutaneous transplanted autologous neurogenically-induced bone marrow-derived mesenchymal stem cells (NIBM-MSCs) in paraplegic dogs without deep pain perception (DPP) secondary to external spinal trauma. Thirteen client owned dogs that had failed in improvement neurologically at least 42 days after conservative management, decompression and decompression-stabilization were included in the study. Each dog received two doses of autologous 5.0 × 106 NIBM-MSCs suspension, which were positive to 2′,3′-Cyclic-nucleotide-3′-phosphodiesterase (CNPase) and Microtubule-associated protein 2 (MAP-2), as well as to Glial fibrillary acidic protein (GFAP) and beta III tubulin. The cells were injected into the spinal cord through the hemilaminectomy or laminectomy defects percutaneously with 21 days interval for 2 times. The results were evaluated using Texas Spinal Cord Injury Scale (TSCIS), somatosensory evoked potentials (SEP) and motor evoked potentials (MEP) at the admission time, cell transplantation procedures and during 2, 5, 7 and 12th months after the second cell transplantation. Improvement after cell transplantation in gait, nociception, proprioception, SEP and MEP results was observed in just 2 cases, and only gait score improvement was seen in 6 cases, and no improvement was recorded in 5 cases. All progresses were observed until 2nd month after the second cell transplantation, however, there was no improvement after this period. In conclusion, percutaneous transplantation of autologous NIBM-MSCs is a promising candidate modality for cases with spinal cord injury after spinal trauma and poor prognosis.

Stem Cell Ophthalmology Treatment Study (SCOTS): bone marrow-derived stem cells in the treatment of Leber's hereditary optic neuropathy.

The Stem Cell Ophthalmology Treatment Study (SCOTS) is currently the largest-scale stem cell ophthalmology trial registered at ClinicalTrials.gov (identifier: NCT01920867). SCOTS utilizes autologous bone marrow-derived stem cells (BMSCs) to treat optic nerve and retinal diseases. Treatment approaches include a combination of retrobulbar, subtenon, intravitreal, intra-optic nerve, subretinal, and intravenous injection of autologous BMSCs according to the nature of the disease, the degree of visual loss, and any risk factors related to the treatments. Patients with Leber's hereditary optic neuropathy had visual acuity gains on the Early Treatment Diabetic Retinopathy Study (ETDRS) of up to 35 letters and Snellen acuity improvements from hand motion to 20/200 and from counting fingers to 20/100. Visual field improvements were noted. Macular and optic nerve head nerve fiber layer typically thickened. No serious complications were seen. The increases in visual acuity obtained in our study were encouraging and suggest that the use of autologous BMSCs as provided in SCOTS for ophthalmologic mitochondrial diseases including Leber's hereditary optic neuropathy may be a viable treatment option.

Neurologic Stem Cell Treatment Study (NEST) using bone marrow derived stem cells for the treatment of neurological disorders and injuries: study protocol for a nonrandomized efficacy trial

Background: A large number of approximately 600 known neurological diseases have no or limited medical interventions; many treatments are temporizing or only marginally effective and have changed little over decades. The Neurologic Stem Cell Treatment Study (NEST) utilizes bone marrow derived stem cells (BMSCs) for neurological diseases and injuries to nervous tissue. Methods/Design: Administration of BMSCs is an established approach for the treatment of neurological diseases and injury with its effectiveness verified in the pre-clinical and clinical studies. BMSCs and the associated bone marrow fraction are posited to have a number of different mechanisms by which they may potentially improve neurological function. The circumventricular organs which lie in the wall of the third ventricle are noteworthy for a minimized or absent blood-brain barrier (BBB) facilitating entry of intravenously provided BMSCs. There is documentation in the literature that intranasal delivery of BMSCs may follow the pathways of the trigeminal nerves, facilitating their entry into the pons, brain parenchyma and cerebral spinal fluid (CSF) for effects on the CNS. The NEST is an open label, non-randomized, efficacy study with two arms. Arm 1 consists of intravenous autologous BMSCs alone; Arm 2 combines intravenous with intranasal application of BMSCs to the lower 1/3 of the nasal mucosa. There will be a total of 300 patients in the study. Endpoints include at least a 10% improvement in neurological function. Discussion: There have been a number of preclinical studies establishing the utility of intravenous and intranasal methods in providing access to the CNS for certain drugs, proteins and cellular elements. Preclinical and clinical studies utilizing BMSCs have shown positive effects in various neurological diseases. It is anticipated that combining these two administration methods for BMSCs delivery to the brain may provide a greater therapeutic response. Trial registration: ClinicalTrials.gov identifier NCT02795052; registered on June 6, 2016. Ethics: This study protocol has been Institutional Review Board (IRB) approved and will be performed in accordance with principles of research ethics set forth in the Belmont Report. Informed consent: Signed informed consent will be obtained from the patients or their guardians.

Neurodegeneration research: From molecules, big animal models to human beings

A connections or interactions among different neural cell types are essential for the correct and efficient functioning of the nervous system during development and regeneration after trauma or degeneration. The aim of my research is to understand the molecular events that mediate communication among neural cells in the nervous system during development, myelination, learning and memory, degeneration and regeneration. These studies have yielded insights into the therapeutic potential of cell signalling molecules to ameliorate or even ablate the detrimental consequences of nervous system injury and neurodegenerative diseases including stroke, traumatic brain injury, spinal cord injury, Alzheimer Disease (AD) and Multiple Sclerosis (MS). Using genome-wide chromatin immunoprecipitation approaches, we found that AICD is specifically recruited to the regulatory regions of several microRNA genes and acts as a transcriptional regulator for miR-663 by which suppresses neuronal differentiation in human neural stem cells. We have generated transgenic pigs expressing mutant G93A hSOD1 and showing hind limb motor defects which are germline transmissible and motor neuron degeneration in doseandage-dependent manners. Furthermore, in a case report we present the treatment of aggressive MS patient with multiple allogenic human umbilical cord-derived mesenchymal stemcell and autologous bone marrow-derived mesenchymal stem cells over a 4 years period. The treatments were tolerated well with no significant adverse events. Clinical and radiological disease appeared to be suppressed following the treatmentsand support the expansion of mesenchymal stem cell transplantation into clinical trials as a potential novel therapy forpatients with aggressive MS.

Assessment of bone marrow-derived Cellular Therapy in progressive Multiple Sclerosis (ACTiMuS): study protocol for a randomised controlled trial.

BackgroundWe have recently completed an evaluation of the safety and feasibility of intravenous delivery of autologous bone marrow in patients with progressive multiple sclerosis (MS). The possibility of repair was suggested by improvement in the neurophysiological secondary outcome measure seen in all participants. The current study will examine the efficacy of intravenous delivery of autologous marrow in progressive MS. Laboratory studies performed in parallel with the clinical trial will further investigate the biology of bone marrow-derived stem cell infusion in MS, including mechanisms underlying repair.Methods/designA prospective, randomised, double-blind, placebo-controlled, stepped wedge design will be employed at a single centre (Bristol, UK). Eighty patients with progressive MS will be recruited; 60 will have secondary progressive disease (SPMS) but a subset (n = 20) will have primary progressive disease (PPMS). Participants will be randomised to either early or late (1 year) intravenous infusion of autologous, unfractionated bone marrow. The placebo intervention is infusion of autologous blood. The primary outcome measure is global evoked potential derived from multimodal evoked potentials. Secondary outcome measures include adverse event reporting, clinical (EDSS and MSFC) and self-assessment (MSIS-29) rating scales, optical coherence tomography (OCT) as well as brain and spine MRI. Participants will be followed up for a further year following the final intervention. Outcomes will be analysed on an intention-to-treat basis.DiscussionAssessment of bone marrow-derived Cellular Therapy in progressive Multiple Sclerosis (ACTiMuS) is the first randomised, placebo-controlled trial of non-myeloablative autologous bone marrow-derived stem cell therapy in MS. It will determine whether bone marrow cell therapy can, as was suggested by the phase I safety study, improve conduction in multiple central nervous system pathways affected in progressive MS. Furthermore, laboratory studies performed in parallel with the clinical trial will inform our understanding of the cellular pharmacodynamics of bone marrow infusion in MS patients and the mechanisms underlying cell therapy.Trial RegistrationISRCTN27232902 Registration date 11/09/2012. NCT01815632 Registration date 19/03/2013

Intravitreal Implantation of Genetically Modified Autologous Bone Marrow-Derived Stem Cells for Treating Retinal Disorders.

A number of retinal degenerative diseases may be amenable to treatment with continuous intraocular delivery of therapeutic agents that cannot be delivered effectively to the retina via systemic or topical administration. Among these disorders are lysosomal storage diseases resulting from deficiencies in soluble lysosomal enzymes. Most cells, including those of the retina, are able to take up these enzymes and incorporate them in active form into their lysosomes. In theory, therefore, continuous intraocular administration of a normal form of a soluble lysosomal enzyme should be able to cure the molecular defect in the retinas of subjects lacking this enzyme. Experiments were conducted to determine whether genetically modified bone marrow-derived stem cells implanted into the vitreous could be used as -vehicles for continuous delivery of such enzymes to the retina. Bone marrow-derived mesenchymal stem cells (MSCs) from normal mice were implanted into the vitreous of mice undergoing retinal degeneration as a result of a mutation in the PPT1 gene. The implanted cells appeared to survive indefinitely in the vitreous without proliferating or invading the retina. This indicates that intravitreal implantation of MSCs is likely a safe means of long-term delivery of proteins synthesized by the implanted cells. Experiments have been initiated to test the efficacy of using genetically modified autologous MSCs to inhibit retinal degeneration in a canine model of neuronal ceroid lipofuscinosis.

Acute promyelocytic leukemia following autologous bone marrow-derived mesenchymal stem cell transplantation for traumatic brain injury: A case report.

Acute myeloid leukemia (AML) is an extremely rare complication that can be observed following mesenchymal stem cells (MSC) transplantation for traumatic brain injury (TBI). Few cases have been reported thus far. The present study reports a case of acute promyelocytic leukemia (APL) following MSC transplantation in a 36-year-old female. The patient presented with a fever and dermatorrhagia with an associative abnormal coagulation test almost 2 months after the MSC transplantation for TBI. The routine blood test, bone marrow (BM) test, and examination of the promyelocytic leukemia/retinoic acid receptor-α and mixed lineage leukemia chimeric genes confirmed the diagnosis of APL and disseminated intravascular coagulation (DIC). The patient was treated with all-trans retinoic acid to induce remission and cryoprecipitate transfusion for the coagulation abnormality. However, the patient succumbed to the DIC shortly after treatment. To the best of our knowledge, this is the first report of the early occurrence of APL in a patient who received autologous BM-derived MSC therapy for TBI.

Effects of autologous bone marrow-derived stem cell mobilization on acute tubular necrosis and cell apoptosis in rats.

The aim of this study was to investigate the effects of stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) on bone marrow-derived stem cell (BMSC) mobilization in rat models of renal ischemia/reperfusion (I/R) injury. In addition, the effects of SCF and G-CSF on cellular apoptosis were explored in order to determine the protective mechanism of the two factors against renal I/R injury. A unilateral renal I/R injury model was established for the model and treatment groups. The treatment and treatment control groups were subcutaneously injected with SCF (200 µg/kg/day) and G-CSF (50 µg/kg/day) 24 h after the establishment of the model for five consecutive days. The total number of leukocytes in the peripheral blood and the cellular percentages of cluster of differentiation (CD)34+, renal CD34+ and apoptotic cells were detected. The total number of leukocytes in the peripheral blood and the percentages of CD34+ cells in the treatment and treatment control groups reached maximum levels on the fifth postoperative day and were significantly higher than those in the normal control and model groups. The number of renal CD34+ cells in the treatment group was significantly increased compared with that in the treatment control and model groups. The apoptotic indices (AIs) of the model and treatment groups were higher than those of the normal control and treatment control groups. The AI of the model group was significantly higher than that of the treatment group. In conclusion, the combined application of SCF and G-CSF can mobilize sufficient numbers of BMSCs and cause cellular 'homing' to the injured site, thus inhibiting apoptosis and promoting the repair of renal tubular injury.

Intramyocardial Autologous Bone Marrow-derived Stem Cells Injection for Ischemic Heart Disease Ineligible for Revascularization: A Systematic Review and Meta-analysis

Intramyocardial autologous bone marrow-derived stem cells injection (IM-BMCs) has been used in patients with ischemic heart disease (IHD) who are ineligible for revascularization; however, the procedure has yielded mixed results. The objective of this meta-analysis was to evaluate the safety and therapeutic benefits of this treatment on a relatively large scale. PubMed, EMBASE, and Cochrane Library databases through September 2014 were searched for randomized clinical trials (RCTs) of IM-BMCs to treat IHD. Outcome measures were defined as mortality after treatment, change in left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV). Weighted mean differences for the changes were estimated with a random-effects model. Nine RCTs were eligible for inclusion. IM-BMCs significantly reduced the risk of mortality (RR, 0.33; 95% CI, 0.17-0.65; p = 0.001). IM-BMCs significantly improved LVEF by 2.57% (95% CI, 0.34-4.80%; p = 0.02) and reduced LVESV by 9.67 mL (95% CI, -16.43 mL to -2.91 mL; p = 0.005). No significant improvement in LVEDV (WMD = 4.73 mL; 95% CI, -7.22 mL to 16.68 mL; p = 0.44) was detected in patients who received IM-BMC therapy. IM-BMC therapy showed clinical safety while being used as stand-alone treatment in IHD with no option of revascularization. The therapeutic efficacy requires further confirmation in large well-powered trials with long-term follow-up.

Effect of Treadmill Exercise and Autologous Bone Marrow-Derived Stem Cells on Cartilage Repair

Effect of Treadmill Exercise and Autologous Bone Marrow-Derived Stem Cells on Cartilage Repair

Efficacy of autologous mesenchymal stem cell transplantation in patients with liver cirrhosis.

Because of several limitations and complications of liver transplantation, new alternative treatment modalities are required for patients with liver cirrhosis. Many study results encourage the use of autologous bone marrow-derived mesenchymal stem cells for liver diseases. In this study, we assessed the impact of autologous mesenchymal stem cell transplantation on liver tissue and liver chemistry. Twenty-five patients with biopsy-proven liver cirrhosis were enrolled in the study. Patients received 1×106 autologous mesenchymal stem cells/kg via a peripheral vein. Biochemical parameters were checked monthly. Periodical radiological screening and liver biopsies before mesenchymal stem cell transplantation were performed after 6 months. Liver specimens were assessed by a pathologist. No side effect was observed and the mesenchymal stem cell transplantation procedure was well tolerated. Twelve patients completed the study. In 8 patients, improvements in Model for End-Stage Liver Disease (MELD) scores were observed. Serum albumin levels markedly increased in the third month. In patients with non-responder hepatitis C, HCV RNA levels both became negative after mesenchymal stem cell transplantation. Histopathological examinations of liver tissues before and at 6 months after transplantation revealed no change in liver tissue regeneration or fibrosis. However, in 5 patients, hepatitis activity index scores decreased. Autologous mesenchymal stem cell transplantation via peripheral vein is safe and feasible. Consecutive liver biopsy examinations suggested that mesenchymal stem cells could not reach the liver in a sufficient amount. Improvement in patients and clearance of HCV RNA may have occurred through immunomodulatory mediators secreted by transplanted mesenchymal stem cells, namely the "endocrine" effect.

Update on clinical trials with autologous bone marrow-derived mesenchymal stem cells secreting neurotrophic factors (MSC-NTF) in patients with amyotrophic lateral sclerosis (ALS)

Update on clinical trials with autologous bone marrow-derived mesenchymal stem cells secreting neurotrophic factors (MSC-NTF) in patients with amyotrophic lateral sclerosis (ALS)

Preparation of autologous bone marrow-derived mesenchymal stem cells (MSCs) for mesenchymal stem cell therapy for canadians with multiple sclerosis (MESCAMS) trial

Preparation of autologous bone marrow-derived mesenchymal stem cells (MSCs) for mesenchymal stem cell therapy for canadians with multiple sclerosis (MESCAMS) trial

Feasibility and safety of intrathecal transplantation of autologous bone marrow mesenchymal stem cells in horses.

BackgroundRecent studies have demonstrated numerous biological properties of mesenchymal stem cells and their potential application in treating complex diseases or injuries to tissues that have difficulty regenerating, such as those affecting the central and peripheral nervous system. Thus, therapies that use mesenchymal stem cells are promising because of their high capacity for self-regeneration, their low immunogenicity, and their paracrine, anti-inflammatory, immunomodulatory, anti-apoptotic and neuroprotective effects. In this context, the purpose of this study was to evaluate the feasibility and safety of intrathecal transplantation of bone marrow-derived mesenchymal stem cells in horses, for future application in the treatment of neurological diseases.ResultsDuring the neurological evaluations, no clinical signs were observed that were related to brain and/or spinal cord injury of the animals from the control group or the treated group. The hematological and cerebrospinal fluid results from day 1 and day 6 showed no significant differences (P > 0.05) between the treated group and the control group. Additionally, analysis of the expression of matrix metalloproteinase (MMP) -2 and −9 in the cerebrospinal fluid revealed only the presence of pro-MMP-2 (latent), with no significant difference (P > 0.05) between the studied groups.ConclusionsThe results of the present study support the hypothesis of the feasibility and safety of intrathecal transplantation of autologous bone marrow-derived mesenchymal stem cells, indicating that it is a promising pathway for cell delivery for the treatment of neurological disorders in horses.

Combined therapy with shock wave and autologous bone marrow-derived mesenchymal stem cells alleviates left ventricular dysfunction and remodeling through inhibiting inflammatory stimuli, oxidative stress & enhancing angiogenesis in a swine myocardial infarction model

BackgroundWe hypothesized that combined therapy with shock wave (SW) and autologous bone marrow-derived mesenchymal stem cells (BMDMSCs) is superior to either therapy alone for alleviating left ventricular (LV) dysfunction. Methods and resultsMale mini-pigs (n=30) equally divided into group 1 (sham control), group 2 [acute myocardial infarction (AMI) by left coronary artery ligation], group 3 (AMI-SW), group 4 (AMI-BMDMSC), and group 5 (AMI-SW-BMDMSC) were sacrificed by day 60 and the hearts were collected for studies. Baseline LV injection fraction [LVEF (%)] and LV chamber size did not differ among the five groups (p>0.5). By day 60, LVEF was highest in group 1 and lowest in group 2, significantly higher in group 5 than that in groups 3 and 4, and significantly higher in group 4 than that in group 3 (p<0.001). Cellular and protein levels of VEGF, CXCR4, and SDF-1α were significantly increased progressively from groups 1 to 5 (all p<0.05). Small vessel number and protein expressions of CD31 and eNOS were highest in groups 1 and 5, lowest in group 2, and significantly higher in group 4 than those in group 3 (p<0.001). Protein (MMP-9, TNF-1α and NF-κB) and cellular (CD14+, CD40+) levels of inflammatory biomarkers, protein expressions of oxidative stress (oxidized protein, NOX-1, NOX-2), apoptosis (Bax, caspase-3, PARP), infarct size, and LV dimensions showed a pattern opposite to that of LVEF among all groups (all p<0.001). ConclusionsCombined SW-BMDMSC therapy is superior to either therapy alone for improving LVEF, reducing infarct size, and inhibiting LV remodeling.

Intraspinal Transplantation of Autologous Neurogenically-Induced Bone Marrow-Derived Mesenchymal Stem Cells in the Treatment of Paraplegic Dogs without Deep Pain Perception Secondary to Intervertebral Disk Disease.

To investigate the effects of neurogenically-induced autologous bone marrow-derived mesenchymal stem cells (NIBM-MSCs) in paraplegic dogs without deep pain perception (DPP) secondary to intervertebral disk disease (IVDD). Seven dogs which could not be improved neurologically with conventional treatment modalities were included in the study. All dogs were diagnosed by magnetic resonance imaging and surgically treated. Each dog received two times a suspension of autologous 5.0x106 NIBM-MSCs, which were positive to CNPase and MAP-2, as well as to GFAP and beta III tubulin into the spinal cord through the hemilaminectomy defect percutaneously, with a 21-day interval. Two months after cell transplantation, there were no changes except for 1 gait score improvement for 1 of the cases. At the 4th month, gait score had improved 1 score in 5 cases, and one score progress was recorded in proprioception and nociception in 1 case. In eight months-followed up 4 cases were evaluated by the same parameter; gait score had improved in 3 cases, and propriception improved in 2 cases, and nociception improved in 3 cases. Our findings suggest that utility of autologous NIBM-MSCs for cases with poor prognosis after IVDD can be a promising approach.

Stem Cell Ophthalmology Treatment Study (SCOTS) for retinal and optic nerve diseases: a preliminary report.

In this report, we present the results of a single patient with optic neuropathy treated within the Stem Cell Ophthalmology Treatment Study (SCOTS). SCOTS is an Institutional Review Board approved clinical trial and is the largest ophthalmology stem cell study registered at the National Institutes of Health to date- www.clinicaltrials.gov Identifier NCT 01920867. SCOTS utilizes autologous bone marrow-derived stem cells in the treatment of optic nerve and retinal diseases. Pre- and post-treatment comprehensive eye exams were independently performed at the Wilmer Eye Institute at the Johns Hopkins Hospital, USA. A 27 year old female patient had lost vision approximately 5 years prior to enrollment in SCOTS. Pre-treatment best-corrected visual acuity at the Wilmer Eye Institute was 20/800 Right Eye (OD) and 20/4,000 Left Eye (OS). Four months following treatment in SCOTS, the central visual acuity had improved to 20/100 OD and 20/40 OS.

Stem Cell Ophthalmology Treatment Study (SCOTS) for retinal and optic nerve diseases: a case report of improvement in relapsing auto-immune optic neuropathy.

We present the results from a patient with relapsing optic neuropathy treated within the Stem Cell Ophthalmology Treatment Study (SCOTS). SCOTS is an Institutional Review Board approved clinical trial and has become the largest ophthalmology stem cell study registered at the National Institutes of Health to date (www.clinicaltrials.gov Identifier NCT 01920867). SCOTS utilizes autologous bone marrow-derived stem cells (BMSCs) for treatment of retinal and optic nerve diseases. Pre-treatment and post-treatment comprehensive eye exams of a 54 year old female patient were performed both at the Florida Study Center, USA and at The Eye Center of Columbus, USA. As a consequence of a relapsing optic neuritis, the patient's previously normal visual acuity decreased to between 20/350 and 20/400 in the right eye and to 20/70 in the left eye. Significant visual field loss developed bilaterally. The patient underwent a right eye vitrectomy with injection of BMSCs into the optic nerve of the right eyeand retrobulbar, subtenon and intravitreal injection of BMSCs in the left eye. At 15 months after SCOTS treatment, the patient's visual acuity had improved to 20/150 in the right eye and 20/20 in the left eye. Bilateral visual fields improved markedly. Both macular thickness and fast retinal nerve fiber layer thickness were maximally improved at 3 and 6 months after SCOTS treatment. The patient also reduced her mycophenylate dose from 1,500 mg per day to 500 mg per day and required no steroid pulse therapy during the 15-month follow up.

Mesenchymal Bone Marrow-derived Stem Cells Transplantation in Patients with HCV Related Liver Cirrhosis.

Background and AimsTo evaluate the effect of intraparenchymal transplantation of mesenchymal bone marrow-derived stem cells (BMSCs) in patients with hepatitis C virus (HCV)-related liver cirrhosis (LC).MethodsMononuclear cells were isolated from patient bone marrow and were passaged several times in vitro in order to reach the required volume. Attributes of the BMSCs were evaluated by the presence of the surface markers CD105+, CD90+, and CD73+. Cells from each passage were evaluated for sterility, and they were transplanted intraparenchymally into liver tissue. Clinical and laboratory data were evaluated and morphological studies of liver biopsy were performed prior to and 6 months after transplantation.ResultsOn clinical evaluation, the general state of these patients was improved at 1 month following transplantation of BMSCs. At 1 and 6 months post-transplantation, jaundice was absent in four (67%) patients. After 6 months, functional hepatic indices were improved, i.e. decrease of ALT and AST activity and bilirubin level. However, these decreases were not statistically different (P>0.05). Expression of CD34 and α-SMA in liver biopsy samples were decreased at 6 months after transplantation, consistent with structural improvements in mitochondria and nuclear compartments.ConclusionsIntraparenchymal transplantation of autologous BMSCs improved the functional condition of the liver, stimulated reparative processes in hepatocytes, and decreased extracellular matrix protein (EMP) count in hepatic tissues of patients with LC. It was well tolerated and was not associated with any complications both during and after BMSC transplantation.

Weft-knitted silk-poly(lactide-co-glycolide) mesh scaffold combined with collagen matrix and seeded with mesenchymal stem cells for rabbit Achilles tendon repair

Natural silk fibroin fiber scaffolds have excellent mechanical properties, but degrade slowly. In this study, we used poly(lactide-co-glycolide) (PLGA, 10:90) fibers to adjust the overall degradation rate of the scaffolds and filled them with collagen to reserve space for cell growth. Silk fibroin-PLGA (36:64) mesh scaffolds were prepared using weft-knitting, filled with type I collagen, and incubated with rabbit autologous bone marrow-derived mesenchymal stem cells (MSCs). These scaffold–cells composites were implanted into rabbit Achilles tendon defects. At 16 weeks after implantation, morphological and histological observations showed formation of tendon-like tissues that expressed type I collagen mRNA and a uniformly dense distribution of collagen fibers. The maximum load of the regenerated Achilles tendon was 58.32% of normal Achilles tendon, which was significantly higher than control group without MSCs. These findings suggest that it is feasible to construct tissue engineered tendon using weft-knitted silk fibroin-PLGA fiber mesh/collagen matrix seeded with MSCs for rabbit Achilles tendon defect repair.