Implantation Of Mesenchymal Stem Cells Research Articles

Autologous mesenchymal stem cell implantation, hydroxyapatite, bone morphogenetic protein-2, and internal fixation for treating critical-sized defects: a translational study

IntroductionCritical-sized defect (CSD) is one of the most challenging cases for orthopaedic surgeons. We aim to explore the therapeutic potential of the combination of bone marrow-derived mesenchymal stem cells (BM-MSCs), hydroxyapatite (HA) granules, bone morphogenetic protein-2 (BMP-2), and internal fixation for treating CSDs.MethodsThis was a translational study performed during the period of January 2012 to 2016. Subjects were patients diagnosed with CSDs who had previously failed surgical attempts. They were treated with the combination of autologous BM-MSCs, HA granules, BMP-2, and mechanical stabilization. Post-operative pain level, functional outcome, defect volume, and radiological healing were evaluated after a minimum follow-up of 12 months.ResultsA total of six subjects were recruited in this study. The pain was significantly reduced in all cases; with the decrease of mean preoperative visual analog scale (VAS) from 4 ± 2.2 to 0 after six month follow-up. Clinical functional outcome percentage increased significantly from 25 ± 13.7 to 70.79 ± 19.5. Radiological healing assessment using Tiedemann score also showed an increase from 0.16 ± 0.4 to 8 ± 3 at one year follow-up. No immunologic nor neoplastic side effects were found.ConclusionsThe combination of autologous BM-MSCs, HA granules, and BMP-2 is safe and remains to be a good option for the definitive treatment for CSD with previous failed surgical attempts. Further studies with a larger sample size are required to be done.

Human umbilical cord mesenchymal stem cells implantation accelerates cutaneous wound healing in diabetic rats via the Wnt signaling pathway

ObjectiveDifficulty in wound healing is one common complication of diabetes mellitus. The study explored whether the therapeutic effect of human umbilical cord mesenchymal stem cells (hUCMSCs) on diabetic ulcer wound was enhanced by the activation of the Wnt signaling pathway.MethodsRat diabetic model was established by intraperitoneal injection of Streptozotocin (STZ). hUCMSCs were purified and seeded on the collagen–chitosan laser drilling acellular dermal matrix (CCLDADM) scaffold, which was subsequently implanted into the cutaneous wound of normal and diabetic rats, followed by daily injection of Wnt signaling pathway agonist (Wnt3a) or antagonist (sFRP3) at the edge of the scaffold. Wound healing was checked on days 7, 14, and 21, and the fibrous tissue deposition, capillaries, and epidermal regeneration at the wound were examined by hematoxylin–eosin staining. The hUCMSCs-CCLDADM scaffold was cultured in vitro and treated with Wnt3a or sFRP3, followed by evaluation of cell proliferation, cell proliferation rate, survival status, and altered protein levels in the Wnt signaling pathway using BrdU staining, CCK-8 assay, live/dead staining, and Western blotting, respectively.ResultsOn days 7 and 14 postoperatively, the speed of wound healing was significantly lower in diabetic rats than that in normal control rats. This phenomenon was significantly improved by the activation of the Wnt signaling pathway that also elevated the fibrous protein deposition and the abundance of capillary in the granulation tissue. Conversely, blockade of Wnt signaling slowed the healing of skin wound in diabetic rats. The activation of Wnt signaling pathway promoted the proliferation and differentiation and decreased the apoptosis of hUCMSCs, thereby elevating the number of living hUCMSCs on the CCLDADM scaffold, while the suppression exerted a contrary effect.ConclusionThe activation of the Wnt signaling pathway promotes the healing of diabetic skin wound by the regulation of proliferation and differentiation of hUCMSCs on the CCLDADM scaffold.

Nanosecond pulsed electric fields enhanced chondrogenic potential of mesenchymal stem cells via JNK/CREB-STAT3 signaling pathway

BackgroundNanosecond pulsed electric fields (nsPEFs) can produce more significant biological effects than traditional electric fields and have thus attracted rising attention in developing medical applications based on short pulse duration and high field strength, such as effective cancer therapy. However, little is known about their effects on the differentiation of stem cells. Furthermore, mechanisms of electric fields on chondrogenic differentiation of mesenchymal stem cells (MSCs) remain elusive, and effects of electric fields on cartilage regeneration need to be verified in vivo. Here, we aimed to study the effects of nsPEFs on chondrogenic differentiation of MSCs in vitro and in vivo and further to explore the mechanisms behind the phenomenon.MethodsThe effects of nsPEF-preconditioning on chondrogenic differentiation of mesenchymal stem cells (MSCs) in vitro were evaluated using cell viability, gene expression, glycosaminoglycan (sGAG) content, and histological staining, as well as in vivo cartilage regeneration in osteochondral defects of rats. Signaling pathways were investigated with protein expression and gene expression, respectively.ResultsnsPEF-preconditioning with proper parameters (10 ns at 20 kV/cm, 100 ns at 10 kV/cm) significantly potentiated chondrogenic differentiation capacity of MSCs with upregulated cartilaginous gene expression and increased matrix deposition through activation of C-Jun NH2-terminal kinase (JNK) and cAMP-response element binding protein (CREB), followed by activation of downstream signal transducer and activator of transcription (STAT3). Implantation of nsPEF-preconditioned MSCs significantly enhanced cartilage regeneration in vivo, compared with implantation of non-nsPEF-preconditioned MSCs.ConclusionThis study demonstrates a unique approach of nsPEF treatment to potentiate the chondrogenic ability of MSCs through activation of JNK/CREB-STAT3 that could have translational potential for MSC-based cartilage regeneration.

Erectile and ejaculatory dysfunction improvement related to spinal cord injury recovery after combination approach of rehabilitation and mesenchymal stem cell implantation

Spinal Cord Injury (SCI) is a devastating condition that often leads to permanent functional and neurological deficits in injured individuals. One of the most overlooked consequences of spinal cord injury is sexual functions, such as erectile and ejaculatory dysfunction. Mesenchymal stem cells (MSCs) have been reported as adjunctive treatment to SCI cases. Some animal studies reported both functional and conductivity improvement after MSCs application. Clinical studies on human has also been conducted in small basis, but so far showed equivocal results.

First Year Results of Subretinal Mesenchymal Stem Cell Implantation in Severe Retinitis Pigmentosa

This study includes one-year results of 14 patients with severe Retinitis Pigmentosa (RP) who had subretinal mesenchymal stem cell (ADMSC) implantation. The highest Visual Acuity (VA) in the study was 20/2000 and 7 of the patients had severe VA loss. The patients received subretinal ADMSCs after total vitrectomy. We observed no systemic complications. There were no ocular complications in 8 patients. Choroidal Neovascular Membrane (CNM) developed in one of the patients and intravitreal anti-VEGF injection was performed. The first six patients had Epiretinal Membrane (ERM) with peripheral tractional retinal detachment and received second vitrectomy. One of the patients experienced mild band keratopathy six months after the treatment and another patient had retrolental fibrous tissue at 1-year follow-up examination. Four patients showed VA gain during the first year. Subretinal implantation of ADMSCs may have some adverse effects and the patients should be followed up carefully. This study clarifies the side effects of the therapy which would enlighten future studies. Further studies with higher number of patients will be necessary to optimize the surgical procedure and to determine the benefits of this therapy.

Vertical ridge augmentation using guided bone regeneration procedure and dental pulp derived mesenchymal stem cells with simultaneous dental implant placement: A histologic study in a sheep model

ObjectivesTo determine the effects of bone graft and dental pulp derived mesenchymal stem cells (DPMSCs) implantation with simultaneous dental implant placement on osteointegration, newly formed bone and vertical bone height histologically and histomorphometrically in a sheep model. Material and methodsA total of 48 implants were divided into three groups. In Group I (n = 16), no material was placed around the implants. In Group II (n = 16), particulate deproteinized bovine bone graft (DBBG) was placed around the implant and in Group III (n = 16), 2 × 106 DPMSCs were placed around the implant with DBBG. All implants were covered with a 20 × 30 mm collagen membrane and the edges of the membrane were fixed with mini screws. The animals were sacrificed 3 and 6 weeks after surgery. Histologic and histomorphometric assessments were performed. ResultsThe area of newly formed bone in Groups I, II, and III were calculated as percentage 2.15 ± 0.22, 11.88 ± 0.77, and 14.50 ± 0.67 respectively after 3 weeks and 3.33 ± 0.37, 18.45 ± 0.33, and 29 ± 1.07 after 6 weeks, respectively (P < 0.05). Three weeks after dental implant placement, the vertical bone length was 0.17 ± 0.02 mm in Group I, 0.89 ± 0.068 mm in Group II and 0.96 ± 0.05 mm in Group III. After 6 weeks, these values were 0.28 ± 0.03 mm, 1.34 ± 0.08 mm, and 1.49 ± 0.08 mm, respectively. There was no significant difference between Groups II and III at 3 and 6 weeks in terms of vertical bone length. ConclusionBone graft and DPMSCs application with dental implant have beneficial effects on newly formed bone and vertical bone height in this experimental sheep model.

Efficacy of stem cells on bone consolidation of distraction osteogenesis in animal models: a systematic review.

Distraction osteogenesis (DO) relies on the recruitment and proliferation of mesenchymal stem cells (MSC) to the target site, where they differentiate into osteoblasts to promote bone formation. Nevertheless, MSC recruitment appears to be slow and limits bone formation in DO defects. Thus, this systematic review aims to evaluate the ability of locally applied MSC to enhance bone formation in DO preclinical models. Databases were searched for quantitative pre-clinical controlled studies that evaluated the effect of local administration of MSC on DO bone formation. Eligible studies were identified and data regarding study characteristics, outcome measures and quality were extracted. Nine studies met the inclusion criteria. Autogenous and xenogenous MSC were used to promote DO bone formation. These included bone marrow-derived MSC, adipose tissue-derived MSC and MSC derived from human exfoliated deciduous teeth. Meta-analysis was not possible due to heterogeneities in study designs. Local MSC implantation was not associated with adverse effects. In 4 out of the 5 studies, locally delivered undifferentiated bone-marrow MSC had a positive effect on DO bone formation. Few studies evaluated the therapeutic effects of MSC from other sources. The adjunct use of biologically active molecules or forced expression of key genes involved in osteogenesis further boosted the ability of bone-marrow MSC to promote DO bone formation. While risk of bias and heterogeneity limited the strength of this systematic review, our results suggest that the use of MSC is safe and may provide beneficial effects on DO bone formation.

The Role of Adipose Derived Mesenchymal Stem Cells (MSCs) to Control Autoimmune Disease

There are 80 types of autoimmune diseases (ADs) with some of the same symptoms, but causes are still unclear. The major treatment of ADs is immunosuppressive drugs but these are not effective and associated with substantial toxicities. Stem cell has demonstrated remarkable effectiveness in halting destructive immune response and restoring the body to level of normal function by providing cellular level repair of damage, increasing blood flow, and reducing inflammation. Adipose tissue is one of the most potent and concentrated source of mesenchymal stem cells (MSCs) as an anti-inflammatory and tissue protecting agent which is promote healing and minimal invasive. This study conducted in 20 patients with ADs (11 women and 9 men) in various age between 22 to 70 years old. Patients treated with autologous adipose-derived MSCs implantation through catheterization. The laboratory analysis result of patients before and after MSCs application in 6 months were measured, include haemoglobin (Hb), leukocytes, erythrocyte sedimentation rate (ESR), protein and blood levels in urine, high sensitivity c-reactive protein (hsCRP), C3 and C4 complement, anti-nuclear antibodies (ANA) and anti-double stranded DNA (anti-dsDNA). MSCs are able to improve the performance of hemoglobin which statistically significant increased (p=0.002). MSCs are able to reduce the inflammatory as shown in the number of leukocytes (p=0.015) and ESR (p=0.031) which statistically significant decreased. MSCs can repair the renal function as shown in no presences of protein and blood in patient’s urine. MSCs are also able to augment the immune response as shown in hsCRP which statistically significant decreased (p&lt;0.001), while C3 and C4 complements statistically significant increased (p&lt;0.001). ANA and anti-dsDNA showed a negative result which means MSCs therapy may give a good response to heal the ADs.

Clinical efficiency of bone marrow mesenchymal stem cell implantation for osteonecrosis of the femoral head: a matched pair control study with simple core decompression

BackgroundTo date, several trials have reported the use of mesenchymal stem cell (MSC) implantation for osteonecrosis of the femoral head (ONFH). However, the clinical outcomes have not been conclusive. This study compared the clinical and radiological results of bone marrow mesenchymal stem cell (BMMSC) implantation with traditional simple core decompression (CD) using a matched pair case–control design.MethodsWe retrospectively reviewed 100 patients with ONFH (106 hips) who had been treated by CD alone (50 patients, 53 hips) and CD + BMMSC implantation (50 patients, 53 hips) between February 2004 and October 2014. We assessed the total hip replacement arthroplasty (THA) conversion rate and ARCO (Association Research Circulation Osseous) stage progression. Survivor rate analysis was performed using the Kaplan–Meier method, and an additional THA was defined as the primary endpoints.ResultsThe mean follow-up period was 4.28 years. There was a difference in the THA conversion rate between the CD (49%) and CD + BMMSC groups (28.3%) (p = 0.028). ARCO stage progression was noted in 20 of 53 hips (37.7%) in the CD group and 19 of 53 hips (35.8%) in the CD + BMMSC group. Among collapsed cases (ARCO stages III and IV), there was no difference in clinical failure rate between the two groups. Conversely, in the pre-collapse cases (ARCO stages I and II), only 6 of 30 hips (20%) progressed to clinical failure in the CD + BMMSC group, whereas 15 of 30 hips (50%) progressed to clinical failure in the CD group (p = 0.014). Kaplan–Meier survival analysis showed a significant difference in the time to failure between the two groups up to 10-year follow-up (log-rank test p = 0.031). There was no significant difference in terms of age (p = 0.87) and gender (p = 0.51) when comparing THA conversion rates between groups. No complication was noted.ConclusionsThese results suggest that implantation of MSCs into the femoral head at an early stage of ONFH lowers the THA conversion rate. However, ARCO stage progression is not affected by this treatment.Trial registrationRetrospectively registered

Tissue engineering the human auricle by auricular chondrocyte-mesenchymal stem cell co-implantation.

Children suffering from microtia have few options for auricular reconstruction. Tissue engineering approaches attempt to replicate the complex anatomy and structure of the ear with autologous cartilage but have been limited by access to clinically accessible cell sources. Here we present a full-scale, patient-based human ear generated by implantation of human auricular chondrocytes and human mesenchymal stem cells in a 1:1 ratio. Additional disc construct surrogates were generated with 1:0, 1:1, and 0:1 combinations of auricular chondrocytes and mesenchymal stem cells. After 3 months in vivo, monocellular auricular chondrocyte discs and 1:1 disc and ear constructs displayed bundled collagen fibers in a perichondrial layer, rich proteoglycan deposition, and elastin fiber network formation similar to native human auricular cartilage, with the protein composition and mechanical stiffness of native tissue. Full ear constructs with a 1:1 cell combination maintained gross ear structure and developed a cartilaginous appearance following implantation. These studies demonstrate the successful engineering of a patient-specific human auricle using exclusively human cell sources without extensive in vitro tissue culture prior to implantation, a critical step towards the clinical application of tissue engineering for auricular reconstruction.

Mesenchymal stem cells loaded with paclitaxel&amp;ndash;poly(lactic-&lt;em&gt;co&lt;/em&gt;-glycolic acid) nanoparticles for glioma-targeting therapy

BackgroundMesenchymal stem cells (MSCs) possess inherent tropism towards tumor cells, and so have attracted increased attention as targeted-therapy vehicles for glioma treatment.PurposeThe objective of this study was to demonstrate the injection of MSCs loaded with paclitaxel (Ptx)-encapsulated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) for orthotopic glioma therapy in rats.MethodsPtx-PLGA NP-loaded MSC was obtained by incubating MSCs with Ptx-PLGA NPs. The drug transfer and cytotoxicity of Ptx-PLGA NP-loaded MSC against tumor cells were investigated in the transwell system. Biodistribution and antitumor activity was evaluated in the orthotopic glioma rats after contralateral injection.ResultsThe optimal dose of MSC-loaded Ptx-PLGA NPs (1 pg/cell Ptx) had little effect on MSC-migration capacity, cell cycle, or multilineage-differentiation potential. Compared with Ptx-primed MSCs, Ptx-PLGA NP-primed MSCs had enhanced sustained Ptx release in the form of free Ptx and Ptx NPs. Ptx transfer from MSCs to glioma cells could induce tumor cell death in vitro. As for distribution in vivo, NP-loaded fluorescent MSCs were tracked throughout the tumor mass for 2 days after therapeutic injection. Survival was significantly longer after contralateral implantation of Ptx-PLGA NP-loaded MSCs than those injected with Ptx-primed MSCs or Ptx-PLGA NPs alone.ConclusionBased on timing and sufficient Ptx transfer from the MSCs to the tumor cells, Ptx-PLGA NP-loaded MSC is effective for glioma treatment. Incorporation of chemotherapeutic drug-loaded NPs into MSCs is a promising strategy for tumor-targeted therapy.

Cell encapsulation enhances antidepressant effect of the mesenchymal stem cells and counteracts depressive-like behavior of treatment-resistant depressed rats

Despite the advances in pharmacological therapies, only the half of depressed patients respond to currently available treatment. Thus, the need for further investigation and development of effective therapies, especially those designed for treatment-resistant depression, has been sorely needed. Although antidepressant effects of mesenchymal stem cells (MSCs) have been reported, the potential benefit of this cell therapy on treatment-resistant depression is unknown. Cell encapsulation may enhance the survival rate of grafted cells, but the therapeutic effects and mechanisms mediating encapsulation of MSCs remain unexplored. Here, we showed that encapsulation enhanced the antidepressant effects of MSCs by attenuating depressive-like behavior of Wistar Kyoto (WKY) rats, which are considered as a promising animal model of treatment-resistant depression. The implantation of encapsulated MSCs (eMSCs) into the lateral ventricle counteracted depressive-like behavior and enhanced the endogenous neurogenesis in the subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampus, whereas the implantation of MSCs without encapsulation or the implantation of eMSCs into the striatum did not show such ameliorative effects. eMSCs displayed robust and stable secretion of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor, fibroblast growth factor-2, and ciliary neurotrophic factor (CNTF), and the implantation of eMSCs into the lateral ventricle activated relevant pathways associated with these growth factors. Additionally, eMSCs upregulated intrinsic expression of VEGF and CNTF and their receptors. This study suggests that the implantation of eMSCs into the lateral ventricle exerted antidepressant effects likely acting via neurogenic pathways, supporting their utility for depression treatment.

Dental Pulp Tissue Engineering Using Mesenchymal Stem Cells: a Review with a Protocol.

Mesenchymal stem cells (MSCs) are adult stem cells that can be isolated from human and animal sources such as rats. Recently, an in vivo protocol for pulp tissue engineering using implantation of bone marrow MSCs into rat pulpotomized molars was established by our research group. This coronal pulp regeneration model showed almost complete regeneration/healing with dentin bridge formation when the cavity was sealed with mineral trioxide aggregate (MTA) to create a biocompatible seal of the pulp. This method is a powerful tool for elucidating the processes of dental pulp tissue regeneration following implantation of MSCs. In the present review, we discuss the literature in the field of dental pulp tissue engineering using MSCs including dental pulp stem cells and stem cells from exfoliated deciduous teeth. In addition, we present a brief step-by-step protocol of the coronal pulp regeneration model focusing on the implantation of rat bone marrow MSCs, biodegradable scaffolds, and hydrogels in pulpotomized rat molars. The protocol may lay the foundation for studies aiming at defining further histological and molecular mechanism of the rat pulp tissue engineering.

Transplantation of BDNF Gene Recombinant Mesenchymal Stem Cells and Adhesive Peptide-modified Hydrogel Scaffold for Spinal Cord Repair.

Mesenchymal Stem Cells (MSCs) are promising candidates for nerve tissue engineering. Brain Derived Neurotrophic Factor (BDNF) secreted by MSCs can function to increase neural differentiation and relieve inflammation response. Gene transfection technology is an efficient strategy to increase the secretion levels of cytokines and enhance cellular functions. However, transfection and in vivo gene expression of environmentally sensitive stem cells have been one of the most challenging subjects due to the requirement in both safety and transfection efficiency. In this study, gene transfection technology was applied to prepare BDNF gene recombinant MSCs based on our previously reported liposomal vector ScreenFect® A. To improve cellular survival and gene expression after in situ implantation of MSCs, an adhesive peptide modified hydrogel scaffold was constructed using hyaluronic acid. The scaffold was optimized and modified with an adhesive peptide PPFLMLLKGSTR. The transfected MSCs exhibited improved cellular survival and sustained gene expression in the three-Dimentional (3D) scaffold in vitro. Compared to untransfected MSCs, gene recombinant MSCs effectively improved spinal tissue integrity, inhibited glial scar formation and alleviated inflammatory response. These effects were found discounted when cells were implanted without the scaffold. The study developed a promising implantation system for therapy of severe spinal cord injury and provided the first understanding of Screenfect® A about its functions on stem cell therapy for nerve tissue repair as well as three-dimentional gene expression.

A new strategy for autologous chondrocyte implantation: autologous mesenchymal stem cell and chondrocyte implantation "first in man" study

A new strategy for autologous chondrocyte implantation: autologous mesenchymal stem cell and chondrocyte implantation "first in man" study

Can photobiomodulation associated with implantation of mesenchymal adipose-derived stem cells attenuate the expression of MMPs and decrease degradation of type II collagen in an experimental model of osteoarthritis?

This study aimed to determine whether photobiomodulation therapy (PBMT) could improve the bioavailability and chondroprotective benefits of mesenchymal stem cells injected into the knees of rats used as an experimental model of osteoarthritis (OA) as well as reduce the expression of matrix metalloproteinases (MMPs) and degradation of type II collagen (COL2-1) in the cartilage. Adipose-derived stem/stromal cells (ADSCs) were collected from three male Fischer 344 rats and characterized by flow cytometry. Fifty female Fischer 344 rats were distributed into five groups of 10 animals each. These groups were as follows: control, OA, OA PBMT, OA ADSC, and OA ADSC PBMT. OA was induced in the animals using a 4% papain solution. Animals from the OA ADSC and OA ADSC PBMT groups received an intra-articular injection of 10 × 106 ADSCs and were treated with PBMT by irradiation (wavelength: 808nm, power: 50mW, energy: 42J, energy density: 71.2J/cm2, spot size: 0.028). Euthanasia was performed 7days after the first treatment. The use of PBMT alone and the injection of ADSCs resulted in downregulation of pro-inflammatory cytokines and MPs in cartilage compared to the OA group. PBMT and ADSCs caused upregulation of tissue inhibitors of MPs 1 and 2 and mRNA and protein expression of COL2-1 in cartilage compared to the OA group. The intra-articular injection of ADSCs and PBMT prevented joint degeneration resulting from COL2-1 degradation and modulated inflammation by downregulating cytokines and MMPs in the OA group.

Combined Transplantation of Mesenchymal Stem Cells and Endothelial Progenitor Cells Restores Cavernous Nerve Injury-Related Erectile Dysfunction

BackgroundWhether combined transplantation of mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) is more effective than transplantation of a single cell type in the restoration of erectile function is unknown. AimTo investigate the effect of combined transplantation of MSCs and EPCs on restoration of erectile function in rats with cavernous nerve injury (CNI). MethodsMSCs were isolated from human bone marrow and EPCs were isolated from human umbilical cord blood. MSCs and EPCs were identified by flow cytometry and in vitro differentiation or immunofluorescence staining. 25 8-week-old male Sprague-Dawley rats were allocated to 1 of 5 groups: sham operation group, bilateral CNI group receiving periprostatic implantation of MSCs plus EPCs, MSCs, EPCs, or phosphate buffered saline (control group). 2 weeks after CNI and treatment, erectile function of rats was measured by electrically stimulating the CN. The penis and major pelvic ganglia were harvested for histologic examinations. RNA and protein levels of neurotrophin factors (vascular endothelial growth factor, nerve growth factor, and brain-derived neurotrophic factor) in mono- or coculture MSCs and EPCs were assessed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. OutcomesIntracavernous pressure and mean arterial pressure were measured to evaluate erectile function. Histologic examinations of the penis and major pelvic ganglia and RNA and protein levels of neurotrophin factors in MSCs and EPCs were performed. ResultsMSCs and EPCs expressed the specified cell markers and exhibited the typical appearance and characteristics. Treatments using MSCs and/or EPCs could increase endothelial and smooth muscle contents of the corpus cavernosum, decrease caspase-3 expression and increase penile neuronal nitric oxide synthase expression, and restore the neural component of the major pelvic ganglia in rats with CNI. Combined transplantation of MSCs and EPCs had a better effect on improving erectile function than single transplantation of MSCs or EPCs. Expression levels of vascular endothelial growth factor and nerve growth factor in coculture MSCs and EPCs were significantly higher than those of primary MSCs or EPCs. Clinical TranslationCombined transplantation of MSCs and EPCs was more effective in restoring erectile function in CNI-related erectile dysfunction models. Strengths and LimitationsThe study, for the 1st time, proved that combined transplantation of MSCs and EPCs was more effective in restoring erectile function in rats with CNI. The rat model might not represent the human condition. ConclusionCombined periprostatic transplantation of MSCs and EPCs could restore erectile function in rats with CNI more effectively. MSCs might restore CN fibers by secreting neurotrophin factors such as vascular endothelial growth factor and nerve growth factor, and EPCs could enhance the paracrine activity of MSCs.Fang J-f, Huang X-n, Han X-y, et al. Combined Transplantation of Mesenchymal Stem Cells and Endothelial Progenitor Cells Restores Cavernous Nerve Injury-Related Erectile Dysfunction. J Sex Med 2018;15:284–295.

Comparative Analysis of Mesenchymal Stem Cells from Bone Marrow, Adipose Tissue, and Dental Pulp as Sources of Cell Therapy for Zone of Stasis Burns

ABSTRACTIntroduction: The implantation of mesenchymal stem cells (MSCs) has been shown to exert benefits for the survival of the zone-of-stasis. However, the clinical experience indicates the importance of selecting the right source and type of stem cells. Therefore, we planned the current study to perform a quantitative comparison of MSCs isolated from three different sources to provide information useful in selection of the optimal source and to see whether critical mechanisms are conserved between different populations. Methods: The protective effects of MSCs derived from bone marrow, adipose tissue and dental pulp were compared in a rat model of thermal trauma. The stasis zones were evaluated 72 h after the burn using histochemistry, immunohistochemistry and biochemistry. Results: Gross evaluation of burn wounds revealed that the differences between the mean percentages of the calculated necrotic areas weren't statistically significant. Semi-quantitative grading of the histopathological findings revealed that there were no significant differences between damage scores. Immunohistochemical assessment of apoptotic and necrotic cell deaths revealed that the differences between the mean numbers of apoptotic and necrotic cells weren't statistically significant. Myeloperoxidase activity was found to be significantly lower in the adipose tissue group. Biochemical and immunohistochemical assessment of tissue malondialdehyde revealed that the differences between the groups weren't statistically significant. Finally, the number of neo-vessels in the dental pulp group was found to be significantly higher. Conclusion: Our findings suggest that bone marrow, adipose tissue and dental pulp may serve as a universal donor MSC source for the prevention of burn wound progression.

Survival Analysis after Core Decompression in Association with Platelet-Rich Plasma, Mesenchymal Stem Cells, and Synthetic Bone Graft in Patients with Osteonecrosis of the Femoral Head.

Purpose The aim of this study was to report the rate of survivorship in patients with osteonecrosis of the femoral head treated with core decompression in association with mesenchymal stem cells (MSCs) implantation, platelet-rich plasma (PRP) injection, and synthetic bone graft. Methods We evaluated 24 hips in 16 patients, according to Ficat classification, treated by core decompression, injection of PRP and MSCs, and backfilling of the core tract with synthetic bone graft. Survivorship was estimated using Kaplan–Meier curves. Results The survivorship of core decompression in association with the procedure is 50% at 75 months of follow-up. The survival rate was 80% for patients in early stage and 28.6% for patients in advanced stage at 75 months. When we compared Kaplan–Meier survival curves of patients in stage III + IV and patients in stage I + II, we noticed that the survival functions are statistically different ( p < 0.05, log-rank test), particularly in stage I + II where we had a greater surviving core decompression, in comparison to patients in stage III + IV. Conclusion This technique is safe and good preliminary results were obtained in patients with early stages of the disease with no reported complications. Level of Evidence Level IV, therapeutic case series.

Engineering Stem and Stromal Cell Therapies for Musculoskeletal Tissue Repair.

Stem cells and tissue-derived stromal cells stimulate the repair of degenerated and injured tissues, motivating a growing number of cell-based interventions in the musculoskeletal field. Recent investigations have indicated that these cells are critical for their trophic and immunomodulatory role in controlling endogenous cells. This Review presents recent clinical advances where stem cells and stromal cells have been used to stimulate musculoskeletal tissue repair, including delivery strategies to improve cell viability and retention. Emerging bioengineering strategies are highlighted, particularly toward the development of biomaterials for capturing aspects of the native tissue environment, altering the healing niche, and recruiting endogenous cells.