• Neuroscience
• Stem cells research

• Hypoxic cultivation
• Mesenchymal stromal cells
• Passage number
• Regenerative medicine
• Reproductive system regeneration
• Single-cell transcriptome profiling
• Tissue source
• Vascular regeneration

• Mesenchymal Stem Cells/cytology
• Mesenchymal Stem Cells/physiology
• Humans
• Umbilical Cord/cytology
• Female
• Adipose Tissue/cytology
• Cells, Cultured
• Chorionic Villi/physiology
• Amnion/cytology
• Cell Differentiation

• Cell therapy
• Cerebral small vessel disease
• Mesenchymal stem cell
• Neurological disorders

• cell therapy
• experimental model
• intracerebral hemorrhage
• stem cells

• Animal models
• ICH
• Stem cells
• Updated, meta-analysis

Non-traumatic intracerebral hemorrhage is a highly destructive intracranial disease with high mortality and morbidity rates. The main risk factors for cerebral hemorrhage include hypertension, amyloidosis, vasculitis, drug abuse, coagulation dysfunction, and genetic factors. Clinically, surviving patients with intracerebral hemorrhage exhibit different degrees of neurological deficits after discharge. In recent years, with the development of regenerative medicine, an increasing number of researchers have begun to pay attention to stem cell and exosome therapy as a new method for the treatment of intracerebral hemorrhage, owing to their intrinsic potential in neuroprotection and neurorestoration. Many animal studies have shown that stem cells can directly or indirectly participate in the treatment of intracerebral hemorrhage through regeneration, differentiation, or secretion. However, considering the uncertainty of its safety and efficacy, clinical studies are still lacking. This article reviews the treatment of intracerebral hemorrhage using stem cells and exosomes from both preclinical and clinical studies and summarizes the possible mechanisms of stem cell therapy. This review aims to provide a reference for future research and new strategies for clinical treatment.

• Exosomes
• Intracerebral hemorrhage
• Mesenchymal stem cells
• Neuroprotection
• Stem cells

Intracerebral hemorrhage (ICH) is a significant cause of death and disabilities. Recently, cell therapies using mesenchymal stem cells have been shown to improve ICH-induced neurobehavioral deficits. Based on these findings, we designed this study to evaluate the therapeutic efficacy and underlying mechanisms by which human amnion-derived stem cells (hAMSCs) would ameliorate neurobehavioral deficits of ICH-bearing hosts.

hAMSCs were induced from amnia obtained by cesarean section and administered intravenously to ICH-bearing mice during the acute phase. The mice were then subject to multitask neurobehavioral tests at the subacute phase. We attempted to optimize the dosage and timing of the hAMSC administrations. In parallel with the hAMSCs, a tenfold higher dose of human adipose-derived stem cells (ADSCs) were used as an experimental control. Specimens were obtained from the ICH lesions to conduct immunostaining, flow cytometry, and Western blotting to elucidate the underlying mechanisms of the hAMSC treatment.

The intravenous administration of hAMSCs to the ICH-bearing mice effectively improved their neurobehavioral deficits, particularly when the treatment was initiated at Day 1 after the ICH induction. Of note, the hAMSCs promoted clinical efficacy equivalent to or better than that of hADSCs at 1/10 the cell number. The systemically administered hAMSCs were found in the ICH lesions along with the local accumulation of macrophages/microglia. In detail, the hAMSC treatment decreased the number of CD11b⁺CD45⁺ and Ly6G⁺ cells in the ICH lesions, while splenocytes were not affected. Moreover, the hAMSC treatment decreased the number of apoptotic cells in the ICH lesions. These results were associated with suppression of the protein expression levels of macrophage-related factors iNOS and TNFα.

Intravenous hAMSC administration during the acute phase would improve ICH-induced neurobehavioral disorders. The underlying mechanism was suggested to be the suppression of subacute inflammation and apoptosis by suppressing macrophage/microglia cell numbers and macrophage functions (such as TNFα and iNOS). From a clinical point of view, hAMSC-based treatment may be a novel strategy for the treatment of ICH.

The online version contains supplementary material available at 10.1186/s12974-022-02411-3.

• Mesenchymal stem cells (MSCs)
• hypoxic preconditioning
• intracerebral hemorrhage (ICH)
• microglia
• pyroptosis

Stroke is one of the major causes of disability and death worldwide. Some treatments for stroke exist, but existing treatment methods have limitations such as difficulty in the regeneration of damaged neuronal cells of the brain. Recently, mesenchymal stem cells (MSCs) have been studied as a therapeutic alternative for stroke, and various preclinical and case studies have been reported.

A 55-year-old man suffered an acute stroke, causing paralysis in the left upper and lower limbs. He intravenously transplanted the minimally manipulated human umbilical cord-derived MSCs (MM-UC-MSCs) twice with an 8-d interval. At 65 wk after transplantation, the patient returned to his previous occupation as a veterinarian with no adverse reactions.

MM-UC-MSCs transplantation potentially treats patients who suffer from acute ischemic stroke.

• Acute ischemic stroke
• Behavioral disorder
• Umbilical cord-derived mesenchymal stem cells
• Allogenic
• Cell therapy
• Minimal manipulation
• Case report

To analyze preclinical bone regeneration studies employing mesenchymal stromal cell (MSC)- derived extracellular vesicles (EVs) and highlight any commonalities in EV biomarker expression, miRNA cargo(s) or pathway activation that will aid in understanding the underlying therapeutic mechanisms.

Articles employing EVs derived from either MSCs or MSC-like osteogenic stromal cells in preclinical bone regeneration studies are included in this review.

EVs derived from a variety of MSC types were able to successfully induce bone formation in preclinical models. Many studies failed to perform in-depth EV characterization. The studies with detailed EV characterization data report very different miRNA cargos, even in EVs isolated from the same species and cell types. Few preclinical studies have analyzed the underlying mechanisms of MSC-EV therapeutic action.

There is a critical need for mechanistic preclinical studies with thorough EV characterization to determine the best therapeutic MSC-EV source for bone regeneration therapies. Issues including controlled EV delivery, large scale production, and proper storage also need to be addressed before EV-based bone regeneration therapies can be translated for clinical bone repair.

•

EVs from different MSC sources successfully regenerate bone in preclinical models.

• Biomaterials
• Bone regeneration
• Extracellular vesicles
• Mesenchymal stromal cells
• Tissue engineering
• miRNA

Intracerebral hemorrhage (ICH) is the most fatal subtype of stroke with high disability and high mortality rates, and there is no effective treatment. The predilection site of ICH is in the area of the basal ganglia and internal capsule (IC), where exist abundant white matter (WM) fiber tracts, such as the corticospinal tract (CST) in the IC. Proximal or distal white matter injury (WMI) caused by intracerebral parenchymal hemorrhage is closely associated with poor prognosis after ICH, especially motor and sensory dysfunction. The pathophysiological mechanisms involved in WMI are quite complex and still far from clear. In recent years, the neuroprotection and repairment capacity of mesenchymal stem cells (MSCs) has been widely investigated after ICH. MSCs exert many unique biological effects, including self-recovery by producing growth factors and cytokines, regenerative repair, immunomodulation, and neuroprotection against oxidative stress, providing a promising cellular therapeutic approach for the treatment of WMI. Taken together, our goal is to discuss the characteristics of WMI following ICH, including the mechanism and potential promising therapeutic targets of MSCs, aiming at providing new clues for future therapeutic strategies.

• cell therapy
• corticospinal tract
• intracerebral hemorrhage
• mesenchymal stem cells
• white matter injury

• cell engineering
• homing
• mesenchymal stem cells
• migration
• neurological disorders
• regeneration
• transplantation

• Humans
• Mesenchymal Stem Cell Transplantation/methods
• Nervous System Diseases/therapy

• different species
• intracerebral hemorrhage
• mesenchymal stem cells
• optimizing strategy
• pathological microenvironment

• Alveolar Bone Loss/diagnostic imaging
• Alveolar Bone Loss/drug therapy
• Animals
• Dipeptides/pharmacology
• Dipeptides/therapeutic use
• Disease Models, Animal
• Male
• Maxillary Diseases/diagnostic imaging
• Maxillary Diseases/drug therapy
• Mice
• Mice, Inbred BALB C
• Osteogenesis/drug effects
• Osteogenesis/physiology
• Periodontitis/diagnostic imaging
• Periodontitis/drug therapy
• Phenylurea Compounds/pharmacology
• Phenylurea Compounds/therapeutic use

• U24 DE026914 NIDCR NIH HHS
• National Institute of Dental and Craniofacial Research

Intracerebral hemorrhage (ICH) is a particularly severe form of stroke, and reactive astrogliosis is a common response following injury to the central nervous system (CNS). Mesenchymal stem cells (MSCs) are reported to promote neurogenesis and alleviate the late side effects in injured brain regions. Gap junctions (Gjs) are abundant in the brain, where the richest connexin (Cx) is Cx43, most prominently expressed in astrocytes. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an essential transcription factor regulating antioxidant reactions. Here, we aimed to explore whether bone marrow MSCs (BM-MSCs) could alleviate brain injury and protect astrocytes from apoptosis, by regulating Cx43 and Nrf2. We validated the effect of BM-MSC transplantation in an ICH model in vivo and in vitro and detected changes using immunofluorescence, as well as protein and mRNA expression of glial fibrillary acidic protein (GFAP), vimentin (VIM), Cx43, Nrf2, and heme oxygenase-1 (HO-1). Our results showed that BM-MSC transplantation attenuated brain injury after ICH and upregulated VIM expression in vivo and in vitro. Additionally, Cx43 upregulation and Nrf2 nuclear translocation were observed in astrocytes cocultured with BM-MSC. Knockdown of Cx43 by siRNA restrained Nrf2 nuclear translocation. Cx43 and Nrf2 had a connection as determined by immunofluorescence and coimmunoprecipitation. We demonstrated that astrocytes undergo astroglial-mesenchymal phenotype switching and have anti-apoptotic abilities after BM-MSC transplantation, where Cx43 upregulation triggers Nrf2 nuclear translocation and promotes its phase II enzyme expression. The Cx43/Nrf2 interaction of astrocytes after BM-MSC transplantation may provide an important therapeutic target in the management of ICH.

• Cx43
• ICH
• MSC
• Nrf2
• astrocytes

• Wharton's jelly
• cell therapy
• hemorrhagic stroke
• intracerebral hemorrhage
• mesenchymal stromal cells
• stem cells

• Matrix metalloproteinase
• cerebrovascular disease
• intracerebral hemorrhage
• outcomes

• Animals
• Cerebral Hemorrhage/complications
• Cerebral Hemorrhage/enzymology
• Cerebral Hemorrhage/pathology
• Hemorrhagic Stroke/enzymology
• Hemorrhagic Stroke/etiology
• Hemorrhagic Stroke/pathology
• Humans
• Matrix Metalloproteinases/metabolism

• Bioactive matrices
• Cellular therapy
• Neural repair
• Tissue-scaffold interactions
• Traumatic Brain Injury

• brain injury
• mesenchymal stem cells
• neural stem cells
• neurogenesis
• stem cell transplantation
• subarachnoid hemorrhage

• Mesenchymal stem cells
• Stroke

• Mayo Clinic Center for Regenerative Medicine Education and Translation Fund

• bone regeneration
• musculoskeletal defects
• strontium folate

• Animals
• Biocompatible Materials/chemical synthesis
• Biocompatible Materials/chemistry
• Bone Regeneration
• Bone and Bones/drug effects
• Bone and Bones/metabolism
• Dental Pulp/cytology
• Folic Acid/chemistry
• Folic Acid/metabolism
• Humans
• Osteogenesis/drug effects
• Osteogenesis/physiology
• Stem Cells/cytology
• Stem Cells/drug effects
• Stem Cells/metabolism
• Strontium/chemistry
• Strontium/metabolism
• Tissue Engineering
• Tissue Scaffolds/chemistry
• Vitamin B 12/chemistry
• Vitamin B 12/metabolism
• Vitamin B 6/chemistry
• Vitamin B 6/metabolism

• MAT201573656-JIN Ministerio de Ciencia e Innovación
• CONACYT (711120) Consejo Nacional de Ciencia y Tecnología
• UNAM-PAPIIT (IA209417) Universidad Autónoma de Mexico

Microglia are the first source of a neuroinflammatory cascade, which seems to be involved in every phase of stroke-related neuronal damage. Two weeks after transient middle cerebral artery occlusion (MCAO), vehicle-treated rats displayed higher numbers of total ionized calcium-binding adaptor molecule 1 (Iba-1)-positive cells, greater cell body areas of Iba-1-positive cells, and higher numbers of hypertrophic Iba-1-positive cells (with a cell body area over 80 μm²) in the ipsilateral ischemic brain regions including the frontal cortex, striatum, and parietal cortex. In addition, MCAO decreased the number of migrating neuroblasts (or DCX- and 5-ethynyl-2′-deoxyuridine-positive cells) in the cortex, subventricular zone, and hippocampus of the ischemic brain, followed by neurological injury (including brain infarct and neurological deficits). Intravenous administration of human umbilical cord–derived mesenchymal stem cells (hUC-MSCs; 1 × 10⁶ or 4 × 10⁶) at 24 h after MCAO reduced neurological injury, decreased the number of hypertrophic microglia/macrophages, and increased the number of newborn neurons in rat brains. Thus, the accumulation of hypertrophic microglia/macrophages seems to be detrimental to neurogenesis after stroke. Treatment with hUC-MSCs preserved adult newborn neurons and reduced functional impairment after transient cerebral ischemia by reducing the number of hypertrophic microglia/macrophages.

• cell therapy
• microglia
• stroke
• umbilical cord mesenchymal stem cells

• intracerebral hemorrhage
• mechanism
• neuroprotective effect
• safety
• stem cell therapy

• Animals
• Cerebral Hemorrhage/therapy
• Embryonic Stem Cells/cytology
• Embryonic Stem Cells/transplantation
• Humans
• Mesenchymal Stem Cell Transplantation
• Neovascularization, Physiologic
• Neural Stem Cells/cytology
• Neural Stem Cells/transplantation
• Neurogenesis
• Stem Cell Transplantation
• Stem Cells/cytology
• Stem Cells/metabolism

• National Natural Science Foundation of China

• NADPH oxidase
• intracerebral hemorrhage
• mesenchymal stromal cells
• preconditioning
• prognosis
• stem cell therapy

• Acetophenones/pharmacology
• Animals
• Cells, Cultured
• Cerebral Hemorrhage/therapy
• Enzyme Inhibitors/pharmacology
• Female
• Humans
• Male
• Mesenchymal Stem Cell Transplantation/methods
• Mesenchymal Stem Cells/drug effects
• Mesenchymal Stem Cells/metabolism
• NADPH Oxidases/antagonists & inhibitors
• Placenta/cytology
• Pregnancy
• Rats
• Rats, Sprague-Dawley
• Tight Junction Proteins/genetics
• Tight Junction Proteins/metabolism

• Colitis
• Cytokines
• FOXP+ Treg
• Feline mesenchymal stem cells
• Immunomodulation
• Inflammatory bowel disease
• PBMC
• Prostaglandin E2

• ANGPT1, angiopoietin-1
• ANGPT2, angiopoietin-2
• ASTM, American Society for Testing and Materials
• Adhesiolysis
• Ang, angiogenin
• C, Celsius
• CD, cluster of differentiation
• CO2, carbon dioxide
• Cryopreserved
• DAB, 3,3′-Diaminobenzidine
• DMEM, Dulbecco’s modified Eagle’s medium
• DMSO, dimethyl sulfoxide
• DPBS, Dulbecco’s phosphate-buffered saline
• ECM, extracellular matrix
• EGF, epidermal growth factor
• EtHd-1, ethidium homodimer-1
• FBS, fetal bovine serum
• FDA, United States Food & Drug Administration
• Fibrosis
• H&E, hematoxylin and eosin
• HGF, hepatocyte growth factor
• HRP, horseradish peroxidase
• IGFBP-1, insulin-like growth factor binding protein-1
• IL-10, interleukin 10
• IL-1RA, interleukin-1 receptor antagonist
• IV, intravenous
• IgG, immunoglobulin
• Inflammation
• MT, Masson’s trichrome
• PBS, phosphate-buffered saline
• PDGF-AA, platelet-derived growth factor AA
• PDGF-BB, platelet-derived growth factor BB
• PLGA, poly(lactic-co-glycolic acid)
• PLGF, placental growth factor
• Placental
• Post-surgical
• SD, standard deviation
• SDF-1α, stromal cell-derived factor 1 alpha
• TIMP-1, tissue inhibitor of metalloproteinases-1
• UT, umbilical cord tissue
• VEGF-D, vascular endothelial growth factor-D
• bFGF, basic fibroblast growth factor
• cAM, calcein acetoxymethyl
• cm, centimeter
• iNOS, inducible nitric oxide synthase
• mg/kg, milligram/kilogram
• mm, millimeter
• rpm, revolutions per minute
• vCUT, viable cryopreserved umbilical tissue

Spinal cord injuries (SCIs) are sustained by an increasing number of patients each year worldwide. The treatment of SCIs has long been a hard nut to crack for doctors around the world. Mesenchymal stem cells (MSCs) have shown benefits for the repair of SCI and recovery of function. Our present study aims to investigate the effects of intravenously infused human umbilical cord blood-derived MSCs (hUCB-MSCs) on functional recovery after subacute spinal cord compression injury of two noncontinuous segments. In addition, we compared the effects of single infusion and repeated intravenous (i.v.) injections on the recovery of spinal cord function.

A total of 43 adult rabbits were randomly divided into four groups: control, single injection (SI), repeated injection at a 3-day (3RI) or repeated injection at a 7-day interval (7RI) groups. Non-immunosuppressed rabbits in the transplantation groups were infused with either a single complete dose or three divided doses of 2 × 10⁶ hUCB-MSCs (3-day or 7-day intervals) on the first day post decompression. Behavioural scores and somatosensory evoked potentials (SEPs) were used to evaluate hindlimb functional recovery. The survival and differentiation of the transplanted human cells and the activation of the host glial and inflammatory reaction in the injured spinal cord were studied by immunohistochemical staining.

Our results showed that hUCB-MSCs survived, proliferated, and primarily differentiated into oligodendrocytes in the injured area. Treatment with hUCB-MSCs reduced the extent of astrocytic activation, increased axonal preservation, potentially promoted axonal regeneration, decreased the number of Iba-1+ and TUNEL+ cells, increased the amplitude and decreased the onset latency of SEPs and significantly promoted functional improvement. However, these effects were more pronounced in the 3RI group compared with the SI and 7RI groups.

Our results suggest that treatment with i.v. injected hUCB-MSCs after subacute spinal cord compression injury of two noncontinuous segments can promote functional recovery through the differentiation of hUCB-MSCs into specific cell types and the enhancement of anti-inflammatory, anti-astrogliosis, anti-apoptotic and axonal preservation effects. Furthermore, the recovery was more pronounced in the rabbits repeatedly injected with cells at 3-day intervals. The results of this study may provide a novel and useful treatment strategy for the transplantation treatment of SCI.

The online version of this article (10.1186/s13287-018-0879-0) contains supplementary material, which is available to authorized users.

• Balloon compression
• Mesenchymal stem cells
• Multilevel spinal injuries
• Repeated injection
• Somatosensory evoked potentials
• Umbilical cord blood

Intracerebral hemorrhage (ICH) is a critical disease, highly associated with mortality and morbidity. Several studies have demonstrated the beneficial effect of mesenchymal stem cells (MSCs) on ICH, mostly focused on their mid-to-long-term effect. Acute hematoma expansion is one of the most important prognostic factors of ICH. We hypothesized that MSCs would decrease mortality and hematoma size in acute ICH, based on the findings of a few recent researches reporting their effect on blood-brain barrier and endothelial integrity. Rat ICH models were made using bacterial collagenase. One hour after ICH induction, the rats were randomly divided into MSC-treated and control groups. Mortality, hematoma volume, ventricular enlargement, brain edema, and degenerating neuron count were compared at 24 hours after ICH induction. Expression of tight junction proteins (ZO-1, occludin) and coagulation factor VII mRNA was also compared. Mortality rate (50% versus 8.3%), hematoma size, ventricular size, hemispheric enlargement, and degenerating neuron count were significantly lower in the MSC-treated group (p = 0.034, 0.038, 0.001, 0.022, and <0.001, resp.), while the expression of ZO-1 and occludin was higher (p = 0.007 and 0.012). Administration of MSCs may prevent hematoma expansion in the hyperacute stage of ICH and decrease acute mortality by enhancing the endothelial integrity of cerebral vasculature.

The potential application of bone marrow stromal cell (BMSC) therapy in stroke has been anticipated due to its immunomodulatory effects. Recently, positron emission tomography (PET) with [¹⁸F]DPA-714, a translocator protein (TSPO) ligand, has become available for use as a neural inflammatory indicator. We aimed to evaluate the effects of BMSC administration after transient middle cerebral artery occlusion (MCAO) using [¹⁸F]DPA-714 PET.

The BMSCs or vehicle were administered intravenously to rat MCAO models at 3 h after the insult. Neurological deficits, body weight, infarct volume, and histology were analyzed. [¹⁸F]DPA-714 PET was performed 3 and 10 days after MCAO.

Rats had severe neurological deficits and body weight loss after MCAO. Cell administration ameliorated these effects as well as the infarct volume. Although weight loss occurred in the spleen and thymus, cell administration suppressed it. In both vehicle and BMSC groups, [¹⁸F]DPA-714 PET showed a high standardized uptake value (SUV) around the ischemic area 3 days after MCAO. Although SUV was increased further 10 days after MCAO in both groups, the increase was inhibited in the BMSC group, significantly. Histological analysis showed that an inflammatory reaction occurred in the lymphoid organs and brain after MCAO, which was suppressed in the BMSC group.

The present results suggest that BMSC therapy could be effective in ischemic stroke due to modulation of systemic inflammatory responses. The [¹⁸F]DPA-714 PET/CT system can accurately demonstrate brain inflammation and evaluate the BMSC therapeutic effect in an imaging context. It has great potential for clinical application.

• Bone marrow stromal cell
• Inflammation
• Ischemic stroke
• Translocator protein
• [18F]DPA-714 PET

• Wnt signaling
• apoptosis
• cell fusion
• mesenchymal stem cells
• tumor

• Transplantation
• human umbilical cord blood mononuclear cells
• middle cerebral artery occlusion

Intracerebral hemorrhage is one of the most common types of cerebrovascular disease in humans and often causes paralysis, a vegetative state and even death. Patients with acute intracerebral hemorrhage are frequently monitored in intensive care units (ICUs). Spontaneous intracerebral hemorrhage is associated with a higher rate of mortality and morbidity than other intracephalic diseases. The expression levels of inflammatory factors have important roles in inflammatory responses indicative of changes in a patient's condition and are therefore important in the monitoring and treatment of affected patients at the ICU as well as the development of therapeutic strategies for acute cerebral hemorrhage. The present study investigated the anti-inflammatory effects of Simvastatin in patients with acute intracerebral hemorrhage at an ICU, and inflammatory factors and cellular changes were systematically analyzed. The plasma concentrations of inflammatory factors, including interleukin (IL)-4, IL-6, IL-8 and IL-10, were evaluated by ELISAs. The plasma concentrations of inflammatory cellular changes were detected by using flow cytometry. The results demonstrated that after Simvastatin treatment of patients with acute cerebral hemorrhage at the ICU, the plasma concentrations of IL-4, IL-6, IL-8 and IL-10 were downregulated compared with those in placebo-treated controls. In addition, Simvastatin treatment at the ICU decreased lymphocytes, granulocytes and mononuclear cells in patients with acute cerebral hemorrhage. The levels of inflammatory factors were associated with brain edema in patients with acute cerebral hemorrhage treated at the ICU. In addition, the amount of bleeding was reduced in parallel with the inflammatory cell plasma concentration of lymphocytes, granulocytes and mononuclear cells. Importantly, Simvastatin treatment produced beneficial outcomes by improving brain edema and reducing the amount of bleeding. In conclusion, the present study demonstrated the efficacy of Simvastatin in treating acute intracerebral hemorrhage and evidenced the association between inflammatory responses and the progress of affected patients at the ICU, thereby providing insight for applying effective therapies for patients with acute intracerebral hemorrhage.

• Simvastatin
• acute intracerebral hemorrhage
• inflammatory responses
• intensive care unit

• Aging
• Neurodegenerative diseases
• Plasticity
• Self-renew
• Stem cell
• Stroke

• Aging/physiology
• Animals
• Brain/metabolism
• Brain/physiopathology
• Humans
• Neurodegenerative Diseases/metabolism
• Neurodegenerative Diseases/therapy
• Neuronal Plasticity/physiology
• Neurons/physiology
• Oxidative Stress/physiology
• Stem Cell Transplantation/methods
• Stroke/metabolism
• Stroke/therapy
• Synapses/metabolism

• I01 BX002346 BLRD VA
• I01 BX003923 BLRD VA
• R01 NS079345 NINDS NIH HHS

• Brain-derived neurotrophic factor (BDNF)
• Human umbilical cord blood-derived mesenchymal stem cells
• Peripheral nerve regeneration

It has always been an ambitious goal in medicine to repair or replace morbid tissues for regaining the organ functionality. This challenge has recently gained momentum through considerable progress in understanding the biological concept of the regenerative potential of stem cells. Routine therapeutic procedures are about to shift towards the use of biological and molecular armamentarium. The potential use of embryonic stem cells and invention of induced pluripotent stem cells raised hope for clinical regenerative purposes; however, the use of these interventions for regenerative therapy showed its dark side, as many health concerns and ethical issues arose in terms of using these cells in clinical applications. In this regard, adult stem cells climbed up to the top list of regenerative tools and mesenchymal stem cells (MSC) showed promise for regenerative cell therapy with a rather limited level of risk. MSC have been successfully isolated from various human tissues and they have been shown to offer the possibility to establish novel therapeutic interventions for a variety of hard-to-noncurable diseases. There have been many elegant studies investigating the impact of MSC in regenerative medicine. This review provides compact information on the role of stem cells, in particular, MSC in regeneration.

• ONOO−
• hypertensive intracerebral hemorrhage
• iNOS
• mesenchymal stromal cells

• Animals
• Disease Models, Animal
• Hemoglobins/metabolism
• Intracranial Hemorrhage, Hypertensive/therapy
• Male
• Mesenchymal Stem Cell Transplantation/methods
• Mesenchymal Stem Cells/physiology
• Random Allocation
• Rats

Generating functional hepatocyte‐like cells (HLCs) from mesenchymal stem cells (MSCs) is of great urgency for bio‐artificial liver support system (BALSS). Previously, we obtained HLCs from human umbilical cord‐derived MSCs by overexpressing seven microRNAs (HLC‐7) and characterized their liver functions in vitro and in vivo. Here, we aimed to screen out the optimal miRNA candidates for hepatic differentiation. We sequentially removed individual miRNAs from the pool and examined the effect of transfection with remainder using RT‐PCR, periodic acid—Schiff (PAS) staining and low‐density lipoprotein (LDL) uptake assays and by assessing their function in liver injury models. Surprisingly, miR‐30a and miR‐1290 were dispensable for hepatic differentiation. The remaining five miRNAs (miR‐122, miR‐148a, miR‐424, miR‐542‐5p and miR‐1246) are essential for this process, because omitting any one from the five‐miRNA combination prevented hepatic trans‐differentiation. We found that HLCs trans‐differentiated from five microRNAs (HLC‐5) expressed high level of hepatic markers and functioned similar to hepatocytes. Intravenous transplantation of HLC‐5 into nude mice with CCl₄‐induced fulminant liver failure and acute liver injury not only improved serum parameters and their liver histology, but also improved survival rate of mice in severe hepatic failure. These data indicated that HLC‐5 functioned similar to HLC‐7 in vitro and in vivo, which have been shown to resemble hepatocytes. Instead of using seven‐miRNA combination, a simplified five‐miRNA combination can be used to obtain functional HLCs in only 7 days. Our study demonstrated an optimized and efficient method for generating functional MSC‐derived HLCs that may serve as an attractive cell alternative for BALSS.

• BALSS
• CCl4
• hepatic differentiation
• mesenchymal stem cells
• miRNA

• BDNF, brain-derived neurotrophic factor
• Brain tissue extracts
• Brain-derived neurotrophic factor
• ELISA, enzyme-linked immunosorbent assay
• FBS, fetal bovine serum
• HUMSCs, human umbilical cord mesenchymal stem cells
• Mesenchymal stem cells
• PROG, progesterone
• Progesterone

• Critical limb ischemia
• Inflammation
• Metabolic syndrome
• Stem cell therapy

• cell therapy
• cord blood banking
• hematopoietic stem cells
• mesenchymal stem cells
• umbilical cord blood

• Animals
• Blood Banking/methods
• Cell- and Tissue-Based Therapy/methods
• Fetal Blood/cytology
• Fetal Blood/physiology
• Hematopoietic Stem Cells/cytology
• Hematopoietic Stem Cells/physiology
• Humans
• Mesenchymal Stem Cells/cytology
• Mesenchymal Stem Cells/physiology

• Human amniotic
• Intracerebral hemorrhage
• Mesenchymal stem cells
• Neurological recovery
• Transplantation

Strontium folate loaded biohybrid scaffolds enhance dental pulp stem cells replication and differentiation, promoting complete regeneration of critical bone defects.