Designing and synthesis of injectable hydrogel based on carboxymethyl cellulose/carboxymethyl chitosan containing QK peptide for femoral head osteonecrosis healing.

Femoral head necrosis is a debilitating disorder that typically caused by impaired blood supply to the hip joint. In this study, a novel injectable hydrogel based on Oxidized Carboxymethyl Cellulose (OCMC)-Carboxymethyl Chitosan (CMCS) polymers containing an angiogenesis stimulator peptide (QK) with a non-toxic crosslinking interaction (Schiff based reaction) was synthesized to enhance angiogenesis following femoral head necrosis in an animal model. The physicochemical features of fabricated injectable hydrogel were analyzed by FTIR, swelling and degradation rate, rheometry, and peptide release. Also, the safety and efficacy were evaluated following an in vitro hydrogel injection study and an avascular necrosis (AVN) animal model. According to the results, the hydrogel exhibited an appropriate swelling ratio and water uptake (>90 %, 24 h) as well as a suitable degradation rate over 21 days accompanied by a continuous peptide release. Also, data showed that hydrogels containing QK peptide boosted the proliferation, differentiation, angiogenesis, and osteogenic potential of both Bone Marrow mesenchymal Stem Cells (BM-MSCs) and human umbilical vein endothelial cells (HUVECs) (****p < 0.0001 and ***p < 0.001, respectively). Furthermore, molecular and histological evaluations significantly demonstrated the overexpression of Runx2, Osteocalcin, Collagen I, VEGF and CD34 genes (**p < 0.01 and ***p < 0.001, respectively), and also femoral head necrosis was effectively prohibited, and more blood vessels were detected in defect area by OCMC-CMCS hydrogel containing QK peptide (bone trabeculae >9000, ***p < 0.001). In conclusion, the findings demonstrate that OCMC-CMCS-QK injectable hydrogel could be considered as an impressive therapeutic construct for femoral head AVN healing.

Synthesis and characterization of a silk fibroin/placenta matrix hydrogel for breast reconstruction.

Reconstructive surgery is a complex and demanding interdisciplinary field. One of the major challenges is the production of sizeable, implantable, inexpensive bioprostheses such as breast implants. In this study, porous hybrid hydrogels were fabricated by a combinatorial method using decellularized human placenta (dHplacenta) and silk fibroin. Histology was used to confirm the acellularity of the dHplacenta. The physio-chemical properties of the hydrogels were evaluated using SEM, FTIR, and rheological assays. The synthesized hydrogels exhibited a uniform 3-D microstructure with an interconnected porous network, and the hybrid hydrogels with a 30/70 ratio had improved mechanical properties compared to the other hydrogels. Hybrid hydrogels were also cultured with adipose-derived mesenchymal stem cells (ADSCs). Liposuction was used to obtain adipose tissue from patients, which was then characterized using flow cytometry and karyotyping. The results showed that CD34 and CD31 were downregulated, whereas CD105 and CD90 were upregulated in ADSCs, indicating a phenotype resembling to that of mesenchymal stem cells from the human bone marrow. Moreover, after re-cellularized hydrogel, the live/dead assay and SEM analysis confirmed that most viability and cellular expansion on the hydrogels contained higher ratios of dHplacenta (30/70) than the other two groups. All these findings recapitulated that the 30/70 dHplacenta/silk fibroin hydrogel can perform as an excellent substrate for breast tissue engineering applications.

In-situ forming hydrogel based on thiolated chitosan/carboxymethyl cellulose (CMC) containing borate bioactive glass for wound healing.

Suitable wound dressings for accelerating wound healing are actively being designed and synthesised. In this study, thiolated chitosan (tCh)/oxidized carboxymethyl cellulose (OCMC) hydrogel containing Cu-doped borate bioglass (BG) was developed as a wound dressing to improve wound healing in a full-thickness skin defect of mouse animal model. Thiolation was used to incorporate thiol groups into chitosan (Ch) to enhance its water solubility and mucoadhesion characteristics. Here, the in situ forming hydrogel was successfully developed using the Schiff-based reaction, and its physio-chemical and antibacterial characteristics were examined. Borate BG was also incorporated in the generated hydrogel to promote angiogenesis and tissue regeneration at the wound site. Investigations of in vitro cytotoxicity assays demonstrated that the synthesised hydrogels showed good biocompatibility and promoted cell growth. These results inspired us to investigate the effectiveness of skin wound healing in a mouse model. On the backs of animals, two full-thickness wounds were created and treated utilising two different treatment conditions: (1) OCMC/tCh hydrogel, (2) OCMC/tCh/borate BG, and (3) control defect. The wound closure ratio, collagen deposition, and angiogenesis activity were measured after 14 days to determine the healing efficacy of the in situ hydrogels used as wound dressings. Overall, the hydrogel containing borate BG was maintained in the defect site, healing efficiency was replicable, and wound healing was apparent. In conclusion, we found consistent angiogenesis, remodelling, and accelerated wound healing, which we propose may have beneficial effects on the repair of skin defects.

The effect of poly I:C or LPS priming on the therapeutic efficacy of mesenchymal stem cells in an adjuvant-induced arthritis rat model.

BACKGROUND: The immunomodulatory properties of mesenchymal stem cells (MSCs) have made them a prospective treatment option for inflammatory and autoimmune disorders. Recent studies have found an association between the immunomodulatory function of MSCs and Toll-like receptors (TLRs). Here, we investigated the effect of priming with lipopolysaccharide (LPS) as TLR4 ligand or polyinosinic:polycytidylic acid (poly I:C) as TLR3 ligand on the immunomodulatory function of adipose-derived MSCs (ADMSCs) in vitro and for the first time in an adjuvant-induced arthritis model (AIA). METHODS: ADMSCs were treated with LPS or poly I:C for 1 h. Splenocyte proliferation in the presence of primed ADMSCs was assessed in vitro using an MTT assay. Next, we investigated the therapeutic effect of primed ADMSCs in vivo. Male Wistar rats were infused with complete Freund's adjuvant (CFA) to develop arthritis and then intraperitoneally treated with not-primed, poly I:C- or LPS-primed ADMSCs. Clinical signs, histopathological alteration, and serum and spleen cytokine levels were analyzed. RESULTS: Poly I:C-primed ADMSCs significantly reduced splenocytes proliferation, while ADMSCs primed with LPS increased splenocytes proliferation. Furthermore, poly I:C-primed ADMSCs significantly alleviated the clinical and histopathological severity and the secretion of inflammatory cytokines associated with Th17/Th1 such as IL-17 and IFN-γ. Poly I:C-primed ADMSCs also increased cytokines IL-10 and TGF-ß. TNF-α and IL-6 Levels were also markedly diminished in the serum of AIA animals treated with poly I:C-primed ADMSCs. In contrast, priming ADMSCs with LPS significantly reduced the therapeutic effect of ADMSCs in AIA animals. CONCLUSION: As a result of these findings, poly I:C priming may be a new technique for improving the therapeutic effects of MSCs in arthritic disorders.

Microorganism-derived biological macromolecules for tissue engineering.

According to literature, certain microorganism productions mediate biological effects. However, their beneficial characteristics remain unclear. Nowadays, scientists concentrate on obtaining natural materials from live creatures as new sources to produce innovative smart biomaterials for increasing tissue reconstruction in tissue engineering and regenerative medicine. The present review aims to introduce microorganism-derived biological macromolecules, such as pullulan, alginate, dextran, curdlan, and hyaluronic acid, and their available sources for tissue engineering. Growing evidence indicates that these materials can be used as biological material in scaffolds to enhance regeneration in damaged tissues and contribute to cosmetic and dermatological applications. These natural-based materials are attractive in pharmaceutical, regenerative medicine, and biomedical applications. This study provides a detailed overview of natural-based biomaterials, their chemical and physical properties, and new directions for future research and therapeutic applications.

Fungal exopolysaccharides: Properties, sources, modifications, and biomedical applications.

Fungal exopolysaccharides (EPSs) are natural biopolymers with diverse potential applications in the biomedical, packaging, cosmetic, and food industries. Fungal EPSs are easy to extract and purify polysaccharides that are biodegradable, biocompatible, with low immunogenicity, bioadhesion ability, antibacterial activity, and contain different reactive groups such as hydroxyl, carboxyl, and amine for chemical modifications. Despite fast progress in identifying and characterization fungal EPSs for biomedical applications, i.e., wound healing, drug, and gene delivery, only a few products have been commercialized based on fungal EPSs. This review critically discusses potential biomedical applications of fungi sourced EPSs in tissue engineering (TE), drug and gene delivery.

Stem cell therapy for COVID-19 pneumonia.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus is a highly contagious microorganism, and despite substantial investigation, no progress has been achieved in treating post-COVID complications. However, the virus has made various mutations and has spread around the world. Researchers have tried different treatments to reduce the side effects of the COVID-19 symptoms. One of the most common and effective treatments now used is steroid therapy to reduce the complications of this disease. Long-term steroid therapy for chronic inflammation following COVID-19 is harmful and increases the risk of secondary infection, and effective treatment remains challenging owing to fibrosis and severe inflammation and infection. Sometimes our immune system can severely damage ourselves in disease. In the past, many researchers have conducted various studies on the immunomodulatory properties of stem cells. This property of stem cells led them to modulate the immune system of autoimmune diseases like diabetes, multiple sclerosis, and Parkinson's. Because of their immunomodulatory properties, stem cell-based therapy employing mesenchymal or hematopoietic stem cells may be a viable alternative treatment option in some patients. By priming the immune system and providing cytokines, chemokines, and growth factors, stem cells can be employed to build a long-term regenerative and protective response. This review addresses the latest trends and rapid progress in stem cell treatment for Acute Respiratory Distress Syndrome (ARDS) following COVID-19.

Osteogenic Potential of Magnesium (Mg)-Doped Multicomponent Bioactive Glass: In Vitro and In Vivo Animal Studies.

The use of bioactive glasses (BGs) has been quite fruitful in hard tissue engineering due to the capability of these materials to bond to living bone. In this work, a melt-derived magnesium (Mg)-doped BG (composition: 45SiO2-3P2O5-26CaO-15Na2O-7MgO-4K2O (mol.%)) was synthesized for being used in bone reconstruction. The prepared BGs were then manufactured as three-dimensional (3D) scaffolds by using the sponge replica approach. The microstructure of the samples was assessed by X-ray diffraction (XRD) and the surface morphology was observed by using scanning electron microscopy (SEM). The in vitro bioactivity and the release of osteo-stimulatory Mg2+ ions from the prepared samples were investigated over 7 days of incubation in simulated body fluids (SBF). In vitro cellular analyses revealed the compatibility of the Mg-doped BGs with human osteosarcoma cells (MG-63 cell line). Moreover, the Mg-doped BGs could induce bone nodule formation in vitro and improve the migratory ability of human umbilical vein endothelial cells (HUVECs). In vivo osteogenic capacity was further evaluated by implanting the BG-derived scaffolds into surgically-created critical-size bone defects in rats. Histological and immunohistological observations revealed an appropriate bone regeneration in the animals receiving the glass-based scaffolds after 12 weeks of surgery. In conclusion, our study indicates the effectiveness of the Mg-doped BGs in stimulating osteogenesis in both in vitro and in vivo conditions.

Human Olfactory Mucosa Stem Cells Delivery Using a Collagen Hydrogel: As a Potential Candidate for Bone Tissue Engineering.

For bone tissue engineering, stem cell-based therapy has become a promising option. Recently, cell transplantation supported by polymeric carriers has been increasingly evaluated. Herein, we encapsulated human olfactory ectomesenchymal stem cells (OE-MSC) in the collagen hydrogel system, and their osteogenic potential was assessed in vitro and in vivo conditions. Collagen type I was composed of four different concentrations of (4 mg/mL, 5 mg/mL, 6 mg/mL, 7 mg/mL). SDS-Page, FTIR, rheologic test, resazurin assay, live/dead assay, and SEM were used to characterize collagen hydrogels. OE-MSCs encapsulated in the optimum concentration of collagen hydrogel and transplanted in rat calvarial defects. The tissue samples were harvested after 4- and 8-weeks post-transplantation and assessed by optical imaging, micro CT, and H&E staining methods. The highest porosity and biocompatibility were confirmed in all scaffolds. The collagen hydrogel with 7 mg/mL concentration was presented as optimal mechanical properties close to the naïve bone. Furthermore, the same concentration illustrated high osteogenic differentiation confirmed by real-time PCR and alizarin red S methods. Bone healing has significantly occurred in defects treated with OE-MSCs encapsulated hydrogels in vivo. As a result, OE-MSCs with suitable carriers could be used as an appropriate cell source to address clinical bone complications.

Synthesis and Characterization of Exopolysaccharide Encapsulated PCL/Gelatin Skin Substitute for Full-Thickness Wound Regeneration.

Loss of skin integrity can lead to serious problems and even death. In this study, for the first time, the effect of exopolysaccharide (EPS) produced by cold-adapted yeast R. mucilaginosa sp. GUMS16 on a full-thickness wound in rats was evaluated. The GUMS16 strain's EPS was precipitated by adding cold ethanol and then lyophilized. Afterward, the EPS with polycaprolactone (PCL) and gelatin was fabricated into nanofibers with two single-needle and double-needle procedures. The rats' full-thickness wounds were treated with nanofibers and Hematoxylin and eosin (H&E) and Masson's Trichrome staining was done for studying the wound healing in rats. Obtained results from SEM, DLS, FTIR, and TGA showed that EPS has a carbohydrate chemical structure with an average diameter of 40 nm. Cell viability assessments showed that the 2% EPS loaded sample exhibits the highest cell activity. Moreover, in vivo implantation of nanofiber webs on the full-thickness wound on rat models displayed a faster healing rate when EPS was loaded into a nanofiber. These results suggest that the produced EPS can be used for skin tissue engineering applications.

Cellulose nanocrystal effect on crystallization kinetics and biological properties of electrospun polycaprolactone.

Mechanical properties of tissue engineering nanofibrous scaffolds are of importance because they not only determine their ease of application, but also influence the environment for cell growth and proliferation. Cellulose nanocrystals (CNCs) are natural renewable nanoparticles that have been widely used for manipulating nanofibers' mechanical properties. In this article, cellulose nanoparticles were incorporated into poly(caprolactone) (PCL) solution, and composite nanofibers were produced. Ozawa-Flynn-Wall (OFW) methodology and X-ray diffraction were used to investigate the effect of CNC incorporation on PCL crystalline structure and its biological properties. Results showed that CNC incorporation up to 1% increases the crystallization activation energy and reduces the crystal volume, while these factors remain constant above this critical concentration. MTT assay and microscopic images of seeded cells on the nanofiber scaffolds indicated increased cell growth on the samples containing CNC. This behavior could be attributed to their greater hydrophilicity, which was confirmed using parallel exponential kinetics (PEK) model fitting to results obtained from dynamic vapor sorption (DVS) studies. Superior performance of CNC containing samples was also confirmed by in vivo implantation on full-thickness wounds. The wound area faded away more rapidly in these samples. H&E and Masson's trichrome staining showed better regeneration and more developed tissues in wounds treated with PCL-CNC1% nanofibers.

Cell Sources in Cardiac Tissue Engineering: Current Choices.

The past decade has evidenced numerous developments in the treatment of heart diseases; however many patients with chronic heart failure suffer from low quality of life. Therapeutic methods, including drug-delivery as well as heart transplantation, have been used to improve quality of life. Cell therapy and tissue engineering have been recently introduced to the field of medicine as a novel therapeutic approach. Treatment of heart diseases has seen novel development through the introduction of cell therapy approaches. Based on the evidence, cell therapy has emerged as a promising therapeutic strategy for the treatment of cardiac diseases. Since the first cell transplant to patients, different types of (stem) cells have been studied. This study aims to provide a comprehensive review of different types of cells and their roles in cardiac cell-based therapy.

Enhanced antimicrobial and full-thickness wound healing efficiency of hydrogels loaded with heparinized ZnO nanoparticles: In vitro and in vivo evaluation.

Nanotechnology-based fabricated wound dressings are known as appropriate substrates to enhance healing in both acute and chronic wounds. These types of materials have the ability to deliver therapeutic agents. In this study, a wound dressing including heparinized zinc oxide nanoparticles in combination with chitosan and poly(vinyl alcohol) was developed to investigate its antibacterial and regenerative properties in a rat model of full thickness skin wounds. By adding nanoparticles, the mechanical strength increased up to twice as compared to the sample without nanoparticles. In addition, heparin release profile follows the Hixson-Crowell release kinetic. Protein adsorption enhanced by adding nanoparticles in hydrogels and the prepared wound dressings were completely biocompatible. In terms of antibacterial activity, the minimum inhibitory concentration decreased by conjugation of heparin on the surface of zinc oxide nanoparticles compared to the non-functionalized nanoparticles, and, this shows the increased antibacterial synergistic effect by adding heparin to nanoparticles. Furthermore, it was found that the heparinized zinc oxide nanoparticles effectively accelerate wound closure, re-epithelialization and decrease collagen deposition compared to other groups after implantation. Hence, the prepared wound dressings have the capacity to significantly enhance healing of acute wounds.

Design and fabrication of polycaprolactone/gelatin composite scaffolds for diaphragmatic muscle reconstruction.

Diaphragmatic wall defects caused by congenital disorders or disease remain a major challenge for physicians worldwide. Polymeric patches have been extensively explored within research laboratories and the clinic for soft tissue and diaphragm reconstruction. However, patch usage may be associated with allergic reaction, infection, granulation, and recurrence of the hernia. In this study, we designed and fabricated a porous scaffold using a combination of 3D printing and freeze-drying techniques. A 3D printed polycaprolactone (PCL) mesh was used to reinforcegelatin scaffolds, representing an advantage over previously reported examples since it provides mechanical strength and flexibility. In vitro studies showed that adherent cells were anchorage-dependent and grew as a monolayer attached to the scaffolds. Microscopic observations indicated better cell attachments for the scaffolds with higher gelatin content as compared with the PCL control samples. Tensile testing demonstrated the mechanical strength of samples was significantly greater than adult diaphragm tissue. The biocompatibility of the specimens was investigated in vivo using a subcutaneous implantation method in Bagg albino adult mice for 20 days, with the results indicating superior cellular behavior and attachment on scaffolds containing gelatin in comparison to pure PCL scaffolds, suggesting that the porous PCL/gelatin scaffolds have potential as biodegradable and flexible constructs for diaphragm reconstruction.

Enhanced healing of a full-thickness wound by a thermoresponsive dressing utilized for simultaneous transfer and protection of adipose-derived mesenchymal stem cells sheet.

To boost the healing process in a full-thickness wound, a simple and efficient strategy based on adipose-derived mesenchymal stem cells (ADSCs) transplantation is described in this work. To increase the chance of ADSCs immobilization in the wound bed and prevent its migration, these cells are fully grown on the surface of a thermoresponsive dressing membrane under in vitro condition. Then, the cells sheet with their secreted extracellular matrix (ECM) is transferred to the damaged skin with the help of this dressing membrane. This membrane remains on wound bed and acts both as a cell sheet transfer vehicle, after external reduction of temperature, and protect wound during the healing process like a common wound dressing. The visual inspection of wounded skin (rat animal model) at selected time intervals shows a higher wound closure rate for ADSCs treated group. For this group of rats, the better quality of reconstructed tissue is approved by results of histological and immunohistochemical analysis since the higher length of the new epidermis, the higher thickness of re-epithelialization layer, a higher level of neovascularization and capillary density, and the least collagen deposition are detected in the healed tissue.

Quantum Dots: A Review from Concept to Clinic.

Quantum dots (QDs) are semiconductor materials that have gained great interest due to their unique characteristics like optical properties. They are extensively being used in different areas, including solar cells, light-emitting diodes, laser technology, as well as biological and biomedical applications. In this review, comprehensive information about different aspects of QDs is provided, including their types and classifications, synthesis approaches, in vitro and in vivo toxicity, biological applications, and potentials in clinical applications. With a focus on the biological aspects, the respective in vitro and in vivo studies are collected and presented. Various surface modifications on QDs are discussed as directly influencing their properties like toxicity and optical abilities. Given the promising results, these materials are clinically used for targeted molecular therapy and imaging. However, there are a large number of questions that should be addressed before the wide application of QDs in a clinical setting. Regarding the existing barriers to QDs, suggestions are given and discussed to present an appropriate route for the clinical use of these materials.

Copper-enriched diamond-like carbon coatings promote regeneration at the bone-implant interface.

There have been several attempts to design innovative biomaterials as surface coatings to enhance the biological performance of biomedical implants. The objective of this study was to design multifunctional Cu/a-C:H thin coating depositing on the Ti-6Al-4V alloy (TC4) via magnetron sputtering in the presence of Ar and CH4 for applications in bone implants. Moreover, the impact of Cu amount and sp2/sp3 ratio on the interior stress, corrosion behavior, mechanical properties, and tribological performance and biocompatibility of the resulting biomaterial was discussed. X-ray photoelectron spectroscopy (XPS) revealed that the sp2/sp3 portion of the coating was enhanced for samples having higher Cu contents. The intensity of the interior stress of the Cu/a-C:H thin bio-films decreased by increase of Cu content as well as the sp2/sp3 ratio. By contrast, the values of Young's modulus, the H3/E2 ratio, and hardness exhibited no significant difference with enhancing Cu content and sp2/sp3 ratio. However, there was an optimum Cu content (36.8 wt.%) and sp2/sp3 ratio (4.7) that it is feasible to get Cu/a-C:H coating with higher hardness and tribological properties. Electrochemical impedance spectroscopy test results depicted significant improvement of Ti-6Al-4V alloy corrosion resistance by deposition of Cu/a-C:H thin coating at an optimum Ar/CH4 ratio. Furthermore, Cu/a-C:H thin coating with higher Cu contents showed better antibacterial properties and higher angiogenesis and osteogenesis activities. The coated samples inhibited the growth of bacteria as compared to the uncoated sample (p < 0.05). In addition, such coating composition can stimulate angiogenesis, osteogenesis and control host response, thereby increasing the success rate of implants. Moreover, Cu/a-C:H thin films encouraged development of blood vessels on the surface of titanium alloy when the density of grown blood vessels was increased with enhancing the Cu amount of the films. It is speculated that such coating can be a promising candidate for enhancing the osseointegration features.

Mineralized Human Amniotic Membrane as a Biomimetic Scaffold for Hard Tissue Engineering Applications.

The human amniotic membrane (HAM) has been viewed as a potential regenerative material for a wide variety of injured tissues because of its collagen-rich content. High degradability of HAM limits its wide practical application in bone tissue engineering. In this study, the natural matrix of the decellularized amniotic membrane was developed by the double diffusion method. The results confirmed a reduction of the amniotic membrane's degradability because of the deposition of calcium and phosphate ions during the double diffusion process. Real-time PCR results showed a high expression of osteogenesis-related genes from adipose-derived mesenchymal stem cells (ADMSCs) cultured on the surface of the developed mineralized amniotic membrane (MAM). Further in vivo experiments were conducted using an MAM preseeded with ADMSCs and a critical-size rat calvarial defect model. Histopathological results confirmed that the MAM + cell sample has excellent potential in bone regeneration.

Decellularized human amniotic membrane: From animal models to clinical trials.

The efficacy of decellularized products for healing of acute and chronic wounds mostly relies on physical and chemical properties, processing methods and host response. Human Amniotic Membrane (HAM) is considered as an effective and highly used wound dressing in clinic. According to the proposed decellularization protocols for developing of HAM, we have compared different protocols to introduce the most efficient methods, which can be used as a functional dermal matrix. In this study, different methods of HAM decellularization were used to achieve an optimal process. After achievement of appropriate decellularized method in vitro the amniotic membrane were examined in term of animal in vivo study and human clinical trial. The results of in vitro and in vivo assay indicate that the HAMs which were prepared with peracetic acid (2 M) had a significantly different in term of GAGs quantification, DNA isolation and quantification, histological assessment, collagen analysis, Cell-Tissue Interaction Study and cytotoxicity (P < 0/05). Tissue samples treated with peracetic acid (2 M) were more acceptable than that of samples prepared with other protocols in terms of preserving natural components and structure and removing of cell fragments. The peracetic acid-processed HAM was further functionally evaluated through in vivo assessments that can further lead to tissue reconstruction within the human host.

Olfactory mucosa stem cells: An available candidate for the treatment of the Parkinson's disease.

Olfactory ectomesenchymal stem cells (OE-MSCs) possess the immunosuppressive activity and regeneration capacity and hold a lot of promises for neurodegenerative disorders treatment. This study aimed to determine OE-MSCs which are able to augment and differentiate into functional neurons and regenerate the CNS and also examine whether the implantation of OE-MSCs in the pars compacta of the substantia nigra (SNpc) can improve Parkinson's symptoms in a rat model-induced with 6-hydroxydopamine. We isolated OE-MSCs from lamina propria in olfactory mucosa and characterized them using flow cytometry and immunocytochemistry. The therapeutic potential of OE-MSCs was evaluated by the transplantation of isolated cells using a rat model of acute SN injury as a Parkinson's disease. Significant behavioral improvement in Parkinsonian rats was elicited by the OE-MSCs. The results demonstrate that the expression of PAX2, PAX5, PITX3, dopamine transporter, and tyrosine hydroxylase was increased by OE-MSCs compared to the control group which is analyzed with real-time polymerase chain reaction technique and immunohistochemical staining. In the outcome, the transplantation of 1,1'-dioctadecyl-3,3,3'3'-tetramethyl indocarbocyanine perchlorate labeled OE-MSCs that were fully differentiated to dopaminergic neurons contribute to a substantial improvement in patients with Parkinson's. Together, our results provide that using OE-MSCs in neurodegenerative disorders might lead to better neural regeneration.