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High frequency plant regeneration from mature seed of elite, recalcitrant Malaysian indica rice ( Oryza sativa L.) CV. MR 219

Sivakumar P, Law YS, Ho CL, Harikrishna JA

Acta. Biol. Hung., 2010 Sep;61(3):313-21.
PMID: 20724277 DOI: 10.1556/ABiol.61.2010.3.7

An efficient in vitro plant regeneration system was established for elite, recalcitrant Malaysian indica rice, Oryza sativa L. CV. MR 219 using mature seeds as explant on Murashige and Skoog and Chu N6 media containing 2,4-dichlorophenoxy acetic acid and kinetin either alone or in different combinations. L-proline, casein hydrolysate and L-glutamine were added to callus induction media for enhancement of embryogenic callus induction. The highest frequency of friable callus induction (84%) was observed in N6 medium containing 2.5 mg l(-1) 2,4-dichlorophenoxy acetic acid, 0.2 mg l(-1) kinetin, 2.5 mg l(-1) L-proline, 300 mg l(-1) casein hydrolysate, 20 mg l(-1) L-glutamine and 30 g l(-1) sucrose under culture in continuous lighting conditions. The maximum regeneration frequency (71%) was observed, when 30-day-old N6 friable calli were cultured on MS medium supplemented with 3 mg l(-1) 6-benzyl aminopurine, 1 mg l(-1) naphthalene acetic acid, 2.5 mg l(-1) L-proline, 300 mg l(-1) casein hydrolysate and 3% maltose. Developed shoots were rooted in half strength MS medium supplemented with 2% sucrose and were successfully transplanted to soil with 95% survival. This protocol may be used for other recalcitrant indica rice genotypes and to transfer desirable genes in to Malaysian indica rice cultivar MR219 for crop improvement.

Matched MeSH terms: Regeneration/physiology
Articular cartilage regeneration with autologous peripheral blood progenitor cells and hyaluronic acid after arthroscopic subchondral drilling: a report of 5 cases with histology

Saw KY, Anz A, Merican S, Tay YG, Ragavanaidu K, Jee CS, et al.

Arthroscopy, 2011 Apr;27(4):493-506.
PMID: 21334844 DOI: 10.1016/j.arthro.2010.11.054

PURPOSE: The purpose of this study was to evaluate the quality of articular cartilage regeneration after arthroscopic subchondral drilling followed by postoperative intraarticular injections of autologous peripheral blood progenitor cells (PBPCs) in combination with hyaluronic acid (HA).
METHODS: Five patients underwent second-look arthroscopy with chondral core biopsy. These 5 patients are part of a larger pilot study in which 180 patients with International Cartilage Repair Society grade III and IV lesions of the knee joint underwent arthroscopic subchondral drilling followed by postoperative intra-articular injections. Continuous passive motion was used on the operated knee 2 hours per day for 4 weeks. Partial weight bearing was observed for the first 6 to 8 weeks. Autologous PBPCs were harvested 1 week after surgery. One week after surgery, 8 mL of the harvested PBPCs in combination with 2 mL of HA was injected intra-articularly into the operated knee. The remaining PBPCs were divided into vials and cryopreserved. A total of 5 weekly intra-articular injections were given.
RESULTS: Second-look arthroscopy confirmed articular cartilage regeneration, and histologic sections showed features of hyaline cartilage. Apart from the minimal discomfort of PBPC harvesting and localized pain associated with the intra-articular injections, there were no other notable adverse reactions.
CONCLUSIONS: Articular hyaline cartilage regeneration is possible with arthroscopic subchondral drilling followed by postoperative intraarticular injections of autologous PBPCs in combination with HA.
LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Matched MeSH terms: Regeneration/physiology*
Articular cartilage regeneration with autologous marrow aspirate and hyaluronic Acid: an experimental study in a goat model

Saw KY, Hussin P, Loke SC, Azam M, Chen HC, Tay YG, et al.

Arthroscopy, 2009 Dec;25(12):1391-400.
PMID: 19962065 DOI: 10.1016/j.arthro.2009.07.011

PURPOSE: The purpose of the study was to determine whether postoperative intra-articular injections of autologous marrow aspirate (MA) and hyaluronic acid (HA) after subchondral drilling resulted in better cartilage repair as assessed histologically by Gill scoring.
METHODS: In a goat model we created a 4-mm full-thickness articular cartilage defect in the stifle joint (equivalent to 1.6 cm in the human knee) and conducted subchondral drilling. The animals were divided into 3 groups: group A (control), no injections; group B (HA), weekly injection of 1 mL of sodium hyaluronate for 3 weeks; and group C (HA + MA), similar to group B but with 2 mL of autologous MA in addition to HA. MA was obtained by bone marrow aspiration, centrifuged, and divided into aliquots for cryopreservation. Fifteen animals were equally divided between the groups and sacrificed 24 weeks after surgery, when the joint was harvested, examined macroscopically and histologically.
RESULTS: Of the 15 animals, 2 from group A had died of non-surgery-related complications and 1 from group C was excluded because of a joint infection. In group A the repair constituted mainly scar tissue, whereas in group B there was less scar tissue, with small amounts of proteoglycan and type II collagen at the osteochondral junction. In contrast, repair cartilage from group C animals showed almost complete coverage of the defect with evidence of hyaline cartilage regeneration. Histology assessed by Gill scoring was significantly better in group C with 1-way analysis of variance yielding an F statistic of 10.611 with a P value of .004, which was highly significant.
CONCLUSIONS: Postoperative intra-articular injections of autologous MA in combination with HA after subchondral drilling resulted in better cartilage repair as assessed histologically by Gill scoring in a goat model.
CLINICAL RELEVANCE: After arthroscopic subchondral drilling, this novel technique may result in better articular cartilage regeneration.

Matched MeSH terms: Regeneration/physiology*
Association between apoptotic neural tissue and cell proliferation in the adult teleost brain

Lim FT, Ogawa S, Parhar IS

Brain Res, 2016 11 01;1650:60-72.
PMID: 27568467 DOI: 10.1016/j.brainres.2016.08.033

Injury to neuronal tissues in the central nervous system (CNS) of mammals results in neural degeneration and sometime leads to loss of function, whereas fish retain a remarkable potential for neuro-regeneration throughout life. Thus, understanding the mechanism of neuro-regeneration in fish CNS would be useful to improve the poor neuro-regenerative capability in mammals. In the present study, we characterized a neuro-regenerative process in the brain of a cichlid, tilapia, Oreochromis niloticus. Morphological observations showed that the damaged brain region (habenula) successfully regrew and reinnervated axonal projections by 60 days post-damage. A fluorescent carbocyanine tracer, DiI tracing revealed a recovery of the major neuronal projection from the regenerated habenula to the interpenduncular nucleus by 60 days post-damage. TUNEL assay showed a significant increase of apoptotic cells (~234%, P<0.01) at one day post-damage, while the number of bromodeoxyuridine (BrdU)-positive proliferative cells were significantly increased (~92%, P<0.05) at 7 days post-damage compared with sham-control fish. To demonstrate a potential role of apoptotic activity in the neuro-regeneration, effects of degenerative neural tissue on cell proliferation were examined in vivo. Implantation of detached neural but not non-neural tissues into the cranial cavity significantly (P<0.01) increased the number of BrdU-positive cells nearby the implantation regions at 3 days after the implantation. Furthermore, local injection of the protein extract and cerebrospinal fluid collected from injured fish brain significantly induced cell proliferation in the brain. These results suggest that factor(s) derived from apoptotic neural cells may play a critical role in the neuro-regeneration in teleost brain.

Matched MeSH terms: Nerve Regeneration/physiology*
Newly regenerated dopaminergic neurons in 6-OHDA-lesioned adult zebrafish brain proliferate in the Olfactory bulb and telencephalon, but migrate to, differentiate and mature in the diencephalon

Vijayanathan Y, Hamzah NM, Lim SM, Lim FT, Tan MP, Majeed ABA, et al.

Brain Res Bull, 2022 Nov;190:218-233.
PMID: 36228872 DOI: 10.1016/j.brainresbull.2022.10.001

In order to understand the biological processes underlying dopaminergic neurons (DpN) regeneration in a 6-hydroxydopamine(6-OHDA)-induced adult zebrafish-based Parkinson's disease model, this study investigated the specific phases of neuroregeneration in a time-based manner. Bromodeoxyuridine (BrdU) was administered 24 h before the harvest of brain tissues at day three, five, seven, nine, 12 and 14 postlesion. Potential migration of proliferative cells was tracked over 14 days postlesion through double-pulse tracking [BrdU and 5-ethynyl-2'-deoxyuridine (EdU)] of cells and immunohistostaining of astrocytes [glial fibrillary acidic protein (GFAP)]. Gene expression of foxa2 and nurr1 (nr4a2a) at day three, nine, 14, 18, 22 and 30 postlesion was quantified using qPCR. Protein expression of foxa2 at day three, seven, 14 and 22 postlesion was validated using the western blot technique. Double labelling [EdU and tyrosine hydroxylase (TH)] of proliferative cells was performed to ascertain their fate after the neuroregeneration processes. It was found that whilst cell proliferation remained unchanged in the area of substantial DpN loss, the ventral diencephalon (vDn), there was a transient increase of cell proliferation in the olfactory bulb (OB) and telencephalon (Tel) seven days postlesion. BrdU-immunoreactive (ir)/ EdU-ir cells and activated astrocytes were later found to be significantly increased in the vDn and its nearby area (Tel) 14 days postlesion. There was a significant but transient downregulation of foxa2 at day three and nine postlesion, and nr4a2a at day three, nine and 14 postlesion. The expression of both genes remained unchanged in the OB and Tel. There was a transient downregulation of foxa2 protein expression at day three and seven postlesion. The significant increase of EdU-ir/ TH-ir cells in the vDn 30 days postlesion indicates maturation of proliferative cells (formed between day five-seven postlesion) into DpN. The present findings warrant future investigation of critical factors that govern the distinctive phases of DpN regeneration.

Matched MeSH terms: Nerve Regeneration/physiology
Fulltext Development and Differentiation of Midbrain Dopaminergic Neuron: From Bench to Bedside

Wang M, Ling KH, Tan JJ, Lu CB

Cells, 2020 06 18;9(6).
PMID: 32570916 DOI: 10.3390/cells9061489

Parkinson's Disease (PD) is a neurodegenerative disorder affecting the motor system. It is primarily due to substantial loss of midbrain dopamine (mDA) neurons in the substantia nigra pars compacta and to decreased innervation to the striatum. Although existing drug therapy available can relieve the symptoms in early-stage PD patients, it cannot reverse the pathogenic progression of PD. Thus, regenerating functional mDA neurons in PD patients may be a cure to the disease. The proof-of-principle clinical trials showed that human fetal graft-derived mDA neurons could restore the release of dopamine neurotransmitters, could reinnervate the striatum, and could alleviate clinical symptoms in PD patients. The invention of human-induced pluripotent stem cells (hiPSCs), autologous source of neural progenitors with less ethical consideration, and risk of graft rejection can now be generated in vitro. This advancement also prompts extensive research to decipher important developmental signaling in differentiation, which is key to successful in vitro production of functional mDA neurons and the enabler of mass manufacturing of the cells required for clinical applications. In this review, we summarize the biology and signaling involved in the development of mDA neurons and the current progress and methodology in driving efficient mDA neuron differentiation from pluripotent stem cells.

Matched MeSH terms: Nerve Regeneration/physiology
Hericium erinaceus (Bull.: Fr.) Pers., a medicinal mushroom, activates peripheral nerve regeneration

Wong KH, Kanagasabapathy G, Naidu M, David P, Sabaratnam V

Chin J Integr Med, 2016 Oct;22(10):759-67.
PMID: 25159861 DOI: 10.1007/s11655-014-1624-2

OBJECTIVE: To study the ability of aqueous extract of Hericium erinaceus mushroom in the treatment of nerve injury following peroneal nerve crush in Sprague-Dawley rats.
METHODS: Aqueous extract of Hericium erinaceus was given by daily oral administration following peroneal nerve crush injury in Sprague-Dawley rats. The expression of protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signaling pathways; and c-Jun and c-Fos genes were studied in dorsal root ganglia (DRG) whereas the activity of protein synthesis was assessed in peroneal nerves by immunohistochemical method.
RESULTS: Peripheral nerve injury leads to changes at the axonal site of injury and remotely located DRG containing cell bodies of sensory afferent neurons. Immunofluorescence studies showed that DRG neurons ipsilateral to the crush injury in rats of treated groups expressed higher immunoreactivities for Akt, MAPK, c-Jun and c-Fos as compared with negative control group (P <0.05). The intensity of nuclear ribonucleoprotein in the distal segments of crushed nerves of treated groups was significantly higher than in the negative control group (P <0.05).
CONCLUSION: H. erinaceus is capable of promoting peripheral nerve regeneration after injury. Potential signaling pathways include Akt, MAPK, c-Jun, and c-Fos, and protein synthesis have been shown to be involved in its action.

Matched MeSH terms: Nerve Regeneration/physiology*
Highly efficient protocol for callogenesis, somagenesis and regeneration of Indica rice plants

Azizi P, Rafii MY, Mahmood M, Hanafi MM, Abdullah SN, Abiri R, et al.

C. R. Biol., 2015 Jul;338(7):463-70.
PMID: 26050100 DOI: 10.1016/j.crvi.2015.04.004

In the present study, we have reported a simple, fast and efficient regeneration protocol using mature embryos as explants, and discovered its effective applicability to a range of Indica rice genotypes. We have considered the response of six varieties in the steps of the regeneration procedure. The results showed that calli were variably developed from the scutellar region of seeds and visible within 6-20 days. The highest and lowest calli induction frequency (70% and 51.66%) and number of induced calli from seeds (14 and 10.33) were observed in MR269 and MRQ74, respectively. The maximum and minimum number (7.66 and 4) and frequency of embryogenic calli (38.33% and 20%) were recorded in MR219 and MRQ74, respectively. However, the highest browning rate was observed in MR84 (87%) and the lowest rate in MRQ50 (46%). The majority of plants regenerated from embryogenic calli were obtained from MRQ50 (54%) and the minimum number of plants from MR84. In this study, the maximum numbers of plantlets were regenerated from the varieties with highest rate of embryogenic calli. Also, various varieties, including MRQ50, MR269, MR276 and MR219, were satisfactorily responding, while MRQ74 and MR84 weakly responded to the procedure. Such a simple, successful and generalized method possesses the potential to become an important tool for crop improvement and functional studies of genes in rice as a model monocot plant.

Matched MeSH terms: Regeneration/physiology*
Current status and prospective application of stem cell-based therapies for spinal cord injury

Das AK, Gopurappilly R, Parhar I

Curr Stem Cell Res Ther, 2011 Jun;6(2):93-104.
PMID: 21190537

Spinal cord injuries (SCIs) are a common form of trauma that leaves a huge trail of morbidity and human suffering in its wake. They occur mostly among the young, causing severe physical, psychological, social and economic burdens. The treatment of this condition has rather been disappointing; most of the management strategies being mainly supportive and prophylactic. In recent years there has been an emerging interest in the use of stem cells to regenerate the nervous tissue that has been damaged or lost. Although there has been much hype and unfounded hope, modest successes have been witnessed, and it is possible that these therapeutic strategies may have much more to offer in the future. This paper will review the current strategies of exploring cell-based therapies, mainly different types of stem cells to treat SCI along with the evidence that has been accumulated over the past decade in a rational bench-to-bedside approach. Furthermore, critical aspects such as the mode of delivery and ethical considerations are also discussed along with feasible suggestions for future translational research to provide a contextual picture of the current state of advancements in this field. The impediments to regeneration in the site of injury are briefly explained along with the benefits and drawbacks of different cell types used in the treatment of this condition. We hope that this review will offer a significant insight into this challenging clinical condition.

Matched MeSH terms: Nerve Regeneration/physiology*
Importance of Stem Cell Migration and Angiogenesis Study for Regenerative Cell-based Therapy: A Review

Aziz NS, Yusop N, Ahmad A

Curr Stem Cell Res Ther, 2020;15(3):284-299.
PMID: 31985383 DOI: 10.2174/1574888X15666200127145923

Stem cells play an essential role in maintaining homeostasis, as well as participating in new tissue regeneration. Over the past 20 years, a great deal of effort has been made to investigate the behaviour of stem cells to enable their potential use in regenerative medicine. However, a variety of biological characteristics are known to exist among the different types of stem cells due to variations in the methodological approach, formulation of cell culture medium, isolation protocol and cellular niches, as well as species variation. In recent years, cell-based therapy has emerged as one of the advanced techniques applied in both medical and clinical settings. Cell therapies aim to treat and repair the injury sites and replace the loss of tissues by stimulating the repair and regeneration process. In order to enable the use of stem cells in regenerative therapies, further characterisation of cell behaviour, in terms of their proliferation and differentiation capacity, mainly during the quiescent and inductive state is regarded as highly necessary. The central focus of regenerative medicine revolves around the use of human cells, including adult stem cells and induced pluripotent stem cells for cell-based therapy. The purpose of this review was to examine the existing body of literature on stem cell research conducted on cellular angiogenesis and migration, to investigate the validity of different strategies and variations of the cell type used. The information gathered within this review may then be shared with fellow researchers to assist in future research work, engaging in stem cell homing for cell-based therapy to enhance wound healing and tissue regeneration process.

Matched MeSH terms: Regeneration/physiology
Organotypic culture of human amnion cells in air-liquid interface as a potential substitute for skin regeneration

Fatimah SS, Chua K, Tan GC, Azmi TI, Tan AE, Abdul Rahman H

Cytotherapy, 2013 Aug;15(8):1030-41.
PMID: 23830235 DOI: 10.1016/j.jcyt.2013.05.003

The aim of the present study was to evaluate the effects of air-liquid interface on the differentiation potential of human amnion epithelial cells (HAECs) to skin-like substitute in organotypic culture.

Matched MeSH terms: Regeneration/physiology*
Skin intervention of fullerene-integrated nanoemulsion in structural and collagen regeneration against skin aging

Ngan CL, Basri M, Tripathy M, Abedi Karjiban R, Abdul-Malek E

Eur J Pharm Sci, 2015 Apr 5;70:22-8.
PMID: 25619806 DOI: 10.1016/j.ejps.2015.01.006

Despite the fact that intrinsic oxidative stress is inevitable, the extrinsic factor such as ultraviolet radiation enhances reactive oxygen species (ROS) generation resulting in premature skin aging. Nanoemulsion was loaded with fullerene, a strong free radical scavenger, and its efficacy to provide protection and regenerative effect against ROS-induced collagen breakdown in human skin was studied. Stable fullerene nanoemulsions were formulated using high shear homogenization and ultrasonic dispersion technique. An open trial was conducted using fullerene nanoemulsion on skin twice a day for 28 days. The mean collagen score significantly increased (P<0.05) from 36.53±4.39 to 48.69±5.46 with 33.29% increment at the end of the treatment. Biophysical characteristics of skin revealed that skin hydration was increased significantly (P<0.05) from 40.91±7.01 to 58.55±6.08 corneometric units (43.12% increment) and the water was able to contain within the stratum corneum without any increased in transepidermal water loss. In the in vitro safety evaluation, fullerene nanoemulsion showed no acute toxicity on 3T3 fibroblast cell line for 48h and no indication of potential dermal irritation. Hence, the fullerene nanoemulsion may assist in protecting collagen from breakdown with cosmeceutical benefit.

Matched MeSH terms: Regeneration/physiology
Delayed liver regeneration in C3H/HeJ mice: possible involvement of haemodynamic and structural changes in the hepatic microcirculation

Marlini M, Mabuchi A, Mallard BL, Hairulhisyam N, Akashi-Takamura S, Harper JL, et al.

Exp Physiol, 2016 12 01;101(12):1492-1505.
PMID: 27634415 DOI: 10.1113/EP085727

NEW FINDINGS: What is the central question of this study? The liver regenerative process is complex and involves a sequence of signalling events, but the possible involvement of structural and haemodynamic changes in vivo during this process has never been explored. What is the main finding and its importance? Normal sinusoidal blood flow and velocity are crucial for a normal regenerative response, and delays in these haemodynamic events resulted in impaired liver regeneration in lipopolysaccharide-insensitive, C3H/HeJ mice. Toll-like receptor 4 signalling is required for restoration of normal liver architecture during the liver regenerative process. Liver regeneration is delayed in mice with a defective Toll-like receptor 4 (TLR4; C3H/HeJ mice) but is normal in TLR4 knockouts (TLR4-/- ). Here, we investigated the possible involvement of structural and haemodynamic changes in vivo in the underlying mechanism. In lipopolysaccharide-sensitive (C3H/HeN and C57BL/6) and lipopolysaccharide-insensitive (C3H/HeJ and TLR4-/- ) mice, a 70% partial hepatectomy (PH) was performed under inhalational anaesthesia. At days 3 and 7 after PH, the hepatic microcirculation was interrogated using intravital microscopy. Delayed liver regeneration was confirmed in C3H/HeJ, but not in C3H/HeN, C57BL/6 (WT) or TLR4-/- mice by liver weight-to-body-weight ratio, the percentage of proliferating cell nuclear antigen (PCNA)-positive cells and mitotic index data. At day 3 after PH, sinusoidal red blood cell velocity increased by 100% in C3H/HeN mice, but by only 40% in C3H/HeJ mice. Estimated sinusoidal blood flow was significantly higher at day 7 after PH in C3H/HeN than in C3H/HeJ mice. The hepatic cord width was significantly larger in C3H/HeN than in C3H/HeJ mice at day 3 and it was significantly larger in TLR4-/- than in C57BL/6 WT mice at day 7 after PH. Hepatocyte nucleus density and functional sinusoidal density was significantly reduced at days 3 and 7 after PH in all mouse strains compared with their zero-time controls. Functional sinusoidal density was significantly lower in C3H/HeJ compared with C3H/HeN mice at day 7 after PH. The present study indicates that altered sinusoidal blood flow and velocity in C3H/HeJ mice may contribute to the observed delay in the regenerative response in these mice. In addition, restoration of normal liver architecture may be delayed in TLR4-/- mice.

Matched MeSH terms: Liver Regeneration/physiology*
Platelet-rich plasma (PRP) enhances bone healing in non-united critical-sized defects: a preliminary study involving rabbit models

Kanthan SR, Kavitha G, Addi S, Choon DS, Kamarul T

Injury, 2011 Aug;42(8):782-9.
PMID: 21329922 DOI: 10.1016/j.injury.2011.01.015

The use of bone grafts in treating non- or delayed unions as the result of large bone loss is well established. However, despite good outcomes, the time to achieve complete union is still considerably long. To overcome this problem, the use of platelet-rich plasma (PRP) has been advocated albeit with varying success. To determine the true effectiveness of PRP in treating non-/delayed unions, a study was conducted using (n=12) rabbit models.

Matched MeSH terms: Bone Regeneration/physiology*
Advancement of Electrospun Nerve Conduit for Peripheral Nerve Regeneration: A Systematic Review (2016-2021)

Lee SY, Thow SY, Abdullah S, Ng MH, Mohamed Haflah NH

Int J Nanomedicine, 2022;17:6723-6758.
PMID: 36600878 DOI: 10.2147/IJN.S362144

Peripheral nerve injury (PNI) is a worldwide problem which hugely affects the quality of patients' life. Nerve conduits are now the alternative for treatment of PNI to mimic the gold standard, autologous nerve graft. In that case, with the advantages of electrospun micro- or nano-fibers nerve conduit, the peripheral nerve growth can be escalated, in a better way. In this systematic review, we focused on 39 preclinical studies of electrospun nerve conduit, which include the in vitro and in vivo evaluation from animal peripheral nerve defect models, to provide an update on the progress of the development of electrospun nerve conduit over the last 5 years (2016-2021). The physical characteristics, biocompatibility, functional and morphological outcomes of nerve conduits from different studies would be compared, to give a better strategy for treatment of PNI.

Matched MeSH terms: Nerve Regeneration/physiology
Spred-2 expression is associated with neural repair of injured adult zebrafish brain

Lim FT, Ogawa S, Parhar IS

J. Chem. Neuroanat., 2016 11;77:176-186.
PMID: 27427471 DOI: 10.1016/j.jchemneu.2016.07.005

Sprouty-related protein-2 (Spred-2) is a negative regulator of extracellular signal-regulated kinases (ERK) pathway, which is important for cell proliferation, neuronal differentiation, plasticity and survival. Nevertheless, its general molecular characteristics such as gene expression patterns and potential role in neural repair in the brain remain unknown. Thus, this study aimed to characterise the expression of spred-2 in the zebrafish brain. Digoxigenin-in situ hybridization showed spred-2 mRNA-expressing cells were mainly seen in the proliferative zones such as the olfactory bulb, telencephalon, optic tectum, cerebellum, and the dorsal and ventral hypothalamus, and most of which were neuronal cells. To evaluate the potential role of spred-2 in neuro-regeneration, spred-2 gene expression was examined in the dorsal telencephalon followed by mechanical-lesion. Real-time PCR showed a significant reduction of spred-2 mRNA levels in the telencephalon on 1-day till 2-days post-lesion and gradually increased to normal levels as compared with intact. Furthermore, to confirm involvement of Spred-2 signalling in the cell proliferation after brain injury, double-labelling of spred-2 in-situ hybridization with immunofluorescence of BrdU and phosphorylated-ERK1/2 (p-ERK1/2), a downstream of Spred-2 was performed. Increase of BrdU and p-ERK1/2 immunoreactive cells suggest that a decrease in spred-2 after injury might associated with activation of the ERK pathway to stimulate cell proliferation in the adult zebrafish brain. The present study demonstrates the possible role of Spred-2 signalling in cell proliferative phase during the neural repair in the injured zebrafish brain.

Matched MeSH terms: Nerve Regeneration/physiology*
Fulltext Sodium phenylbutyrate inhibits Schwann cell inflammation via HDAC and NFκB to promote axonal regeneration and remyelination

Yadav A, Huang TC, Chen SH, Ramasamy TS, Hsueh YY, Lin SP, et al.

J Neuroinflammation, 2021 Oct 16;18(1):238.
PMID: 34656124 DOI: 10.1186/s12974-021-02273-1

BACKGROUND: Epigenetic regulation by histone deacetylases (HDACs) in Schwann cells (SCs) after injury facilitates them to undergo de- and redifferentiation processes necessary to support various stages of nerve repair. Although de-differentiation activates the synthesis and secretion of inflammatory cytokines by SCs to initiate an immune response during nerve repair, changes in either the timing or duration of prolonged inflammation mediated by SCs can affect later processes associated with repair and regeneration. Limited studies have investigated the regulatory processes through which HDACs in SCs control inflammatory cytokines to provide a favorable environment for peripheral nerve regeneration.
METHODS: We employed the HDAC inhibitor (HDACi) sodium phenylbutyrate (PBA) to address this question in an in vitro RT4 SC inflammation model and an in vivo sciatic nerve transection injury model to examine the effects of HDAC inhibition on the expression of pro-inflammatory cytokines. Furthermore, we assessed the outcomes of suppression of extended inflammation on the regenerative potential of nerves by assessing axonal regeneration, remyelination, and reinnervation.
RESULTS: Significant reductions in lipopolysaccharide (LPS)-induced pro-inflammatory cytokine (tumor necrosis factor-α [TNFα]) expression and secretion were observed in vitro following PBA treatment. PBA treatment also affected the transient changes in nuclear factor κB (NFκB)-p65 phosphorylation and translocation in response to LPS induction in RT4 SCs. Similarly, PBA mediated long-term suppressive effects on HDAC3 expression and activity. PBA administration resulted in marked inhibition of pro-inflammatory cytokine secretion at the site of transection injury when compared with that in the hydrogel control group at 6-week post-injury. A conducive microenvironment for axonal regrowth and remyelination was generated by increasing expression levels of protein gene product 9.5 (PGP9.5) and myelin basic protein (MBP) in regenerating nerve tissues. PBA administration increased the relative gastrocnemius muscle weight percentage and maintained the intactness of muscle bundles when compared with those in the hydrogel control group.
CONCLUSIONS: Suppressing the lengthened state of inflammation using PBA treatment favors axonal regrowth and remyelination following nerve transection injury. PBA treatment also regulates pro-inflammatory cytokine expression by inhibiting the transcriptional activation of NFκB-p65 and HDAC3 in SCs in vitro.

Matched MeSH terms: Nerve Regeneration/physiology*
Transplantation of human dental pulp stem cells: enhance bone consolidation in mandibular distraction osteogenesis

Alkaisi A, Ismail AR, Mutum SS, Ahmad ZA, Masudi S, Abd Razak NH

J Oral Maxillofac Surg, 2013 Oct;71(10):1758.e1-13.
PMID: 24040948 DOI: 10.1016/j.joms.2013.05.016

The main aim of the present study was to evaluate the capacity of stem cells from human exfoliated deciduous teeth (SHED) to enhance mandibular distraction osteogenesis (DO) in rabbits.

Matched MeSH terms: Bone Regeneration/physiology
Effect of different calcium phosphate scaffold ratios on odontogenic differentiation of human dental pulp cells

AbdulQader ST, Kannan TP, Rahman IA, Ismail H, Mahmood Z

Mater Sci Eng C Mater Biol Appl, 2015 Apr;49:225-233.
PMID: 25686943 DOI: 10.1016/j.msec.2014.12.070

Calcium phosphate (CaP) scaffolds have been widely and successfully used with osteoblast cells for bone tissue regeneration. However, it is necessary to investigate the effects of these scaffolds on odontoblast cells' proliferation and differentiation for dentin tissue regeneration. In this study, three different hydroxyapatite (HA) to beta tricalcium phosphate (β-TCP) ratios of biphasic calcium phosphate (BCP) scaffolds, BCP20, BCP50, and BCP80, with a mean pore size of 300μm and 65% porosity were prepared from phosphoric acid (H2PO4) and calcium carbonate (CaCO3) sintered at 1000°C for 2h. The extracts of these scaffolds were assessed with regard to cell viability and differentiation of odontoblasts. The high alkalinity, more calcium, and phosphate ions released that were exhibited by BCP20 decreased the viability of human dental pulp cells (HDPCs) as compared to BCP50 and BCP80. However, the cells cultured with BCP20 extract expressed high alkaline phosphatase activity and high expression level of bone sialoprotein (BSP), dental matrix protein-1 (DMP-1), and dentin sialophosphoprotein (DSPP) genes as compared to that cultured with BCP50 and BCP80 extracts. The results highlighted the effect of different scaffold ratios on the cell microenvironment and demonstrated that BCP20 scaffold can support HDPC differentiation for dentin tissue regeneration.

Matched MeSH terms: Regeneration/physiology
Dental stem cells as an alternative source for cardiac regeneration

Xin LZ, Govindasamy V, Musa S, Abu Kasim NH

Med Hypotheses, 2013 Oct;81(4):704-6.
PMID: 23932760 DOI: 10.1016/j.mehy.2013.07.032

Dental tissues contains stem cells or progenitors that have high proliferative capacity, are clonogenic in vitro and demonstrate the ability to differentiate to multiple type cells involving neurons, bone, cartilage, fat and smooth muscle. Numerous experiments have demonstrated that the multipotent stem cells are not rejected by immune system and therefore it may be possible to use these cells in allogeneic settings. In addition, these remarkable cells are easily abundantly available couple with less invasive procedure in isolating comparing to bone marrow aspiration. Here we proposed dental stem cells as candidate for cardiac regeneration based on its immature characteristic and propensity towards cardiac lineage via PI3-Kinase/Aktsignalling pathway.

Matched MeSH terms: Regeneration/physiology*

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