Transplantation of olfactory mucosa mesenchymal stromal cells repairs spinal cord injury by inducing microglial polarization.

STUDY DESIGN: Animal studies OBJECTIVES: To evaluate the therapeutic effect of olfactory mucosa mesenchymal stem cell (OM-MSCs) transplantation in mice with spinal cord injury (SCI) and to explore the mechanism by which OM-MSCs inhibit neuroinflammation and improve SCI. SETTING: Xiangya Hospital, Central South University; Affiliated Hospital of Guangdong Medical University. METHODS: Mice (C57BL/6, female, 6-week-old) were randomly divided into sham, SCI, and SCI + OM-MSC groups. The SCI mouse model was generated using Allen's method. OM-MSCs were immediately delivered to the lateral ventricle after SCI using stereotaxic brain injections. One day prior to injury and on days 1, 5, 7, 14, 21, and 28 post-injury, the Basso Mouse Scale and Rivlin inclined plate tests were performed. Inflammation and microglial polarization were evaluated using histological staining, immunofluorescence, and qRT-PCR. RESULTS: OM-MSCs originating from the neuroectoderm have great potential in the management of SCI owing to their immunomodulatory effects. OM-MSCs administration improved motor function, alleviated inflammation, promoted the transformation of the M1 phenotype of microglia into the M2 phenotype, facilitated axonal regeneration, and relieved spinal cord injury in SCI mice. CONCLUSIONS: OM-MSCs reduced the level of inflammation in the spinal cord tissue, protected neurons, and repaired spinal cord injury by regulating the M1/M2 polarization of microglia.

Targeting autophagy receptors OPTN and SQSTM1 as a novel therapeutic strategy for osteoporosis complicated with Alzheimer's disease.

Alzheimer's disease (AD) is a common degenerative disease among the elderly population. In addition to cognitive impairment, AD is often accompanied by behavioral manifestations. However, little attention has been paid to changes in bone metabolism and related mechanisms in patients with AD. We found that AD mice (APPswe/PS1dE9) had reduced bone density, weakened bone strength, and amyloid beta (Aß) deposition in the bone tissue. It was further found that targeting autophagy receptors Optineurin (OPTN) and Sequestosome 1 (SQSTM1) increased bone density and bone strength in AD mice, promoted the clearance of Aß in the bone tissue, and maintained bone homeostasis. Our study suggests that abnormal Aß deposition may be the co-pathogenesis of AD and osteoporosis (OP). Targeting OPTN and SQSTM1 has a dual-functional effect of alleviating both AD and OP through selective autophagy that specifically targets Aß for clearance. Therapeutic strategies targeting autophagy may help guide the treatment of patients with AD complicated with OP.

Neutralizing peripheral circulating IL1ß slows the progression of ALS in a lentivirus-infected OPTNE478G mouse model.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is irreversible and fatal within 3-5 years, with limited options for treatment. It is imperative to develop a symptom-based treatment that may increase the survival of ALS patients and improve their quality of life. Inflammation status, especially elevated interleukin 1ß (IL1ß), has been reported to play a critical role in ALS progression. Our study determined that neutralizing circulating IL1ß slows down the progression of ALS in an ALS mouse model. METHODS: The ALS mouse model was developed by microinjection of lentivirus-carrying OPTNE478G (optineurin, a mutation from ALS patients) into the intra-motor cortex of mice. Peripheral circulating IL1ß was neutralized by injecting anti-IL1ß antibody into the tail vein. Enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR) were carried out to determine the protein and gene expression levels of IL1ß. TUNEL assay was used to assess the neural cell death. Immunofluorescent staining of MAP2 and CASP3 was accomplished to evaluate neuronal cell apoptosis. Glial fibrillary acidic protein staining was performed to analyze the number of astrocytes. Rotarod test, grip strength test, balance beam test, and footprint test were conducted to assess the locomotive function after anti-IL1ß treatment. RESULTS: The model revealed that neuroinflammation contributes to ALS progression. ALS mice exhibited elevated neuroinflammation and IL1ß secretion. After anti-IL1ß treatment, ALS mice revealed decreased neural cell death and astrogliosis and gained improved muscle strength and motor ability. CONCLUSIONS: Blocking IL1ß is a promising strategy to slow down the progression of ALS.

Transplantation of Nasal Olfactory Mucosa Mesenchymal Stem Cells Benefits Alzheimer's Disease.

Alzheimer's disease (AD) is a common neurodegenerative disease that contributes to 60-70% of dementia in elderly people and is currently incurable. Current treatments only relieve the symptoms of AD and slow its progression. Achieving effective neural regeneration to ameliorate cognitive impairment is a major challenge in the treatment of AD. For the first time, we alleviated symptoms of AD in APPswe/PS1dE9 mice (hereafter referred to as AD mice) by transplantation of olfactory mucosa mesenchymal stem cells (OM-MSCs). Our study demonstrated that OM-MSC transplantation promotes amyloid-ß (Aß) clearance, downregulates the inflammatory response, and increases the M2/M1 ratio; OM-MSCs promote the conversion of BV2 (microglia) from M1 to M2 and also Aß clearance in SH-SY5YAPPswe (AD cell model). OM-MSC-transplanted AD mice show improved cognitive learning and locomotive behavior. Our study suggests that OM-MSC transplantation could alleviate the symptoms of AD and promote Aß clearance through immunomodulation, thus demonstrating the great potential and social value of OM-MSC treatment for AD patients.