Regenerative Growth Research Articles

Clinical development and proof of principle testing of new regenerative vascular endothelial growth factor-D therapy for refractory angina: rationale and design of the phase 2 ReGenHeart trial

BackgroundDespite tremendous therapeutic advancements, a significant proportion of coronary artery disease patients suffer from refractory angina pectoris, that is, quality-of-life-compromising angina that is non-manageable with established pharmacological and interventional treatment...

Inhibition of angiogenesis and regenerative lung growth in Lepob/ob mice through adiponectin-VEGF/VEGFR2 signaling.

Obesity is associated with impairment of wound healing and tissue regeneration. Angiogenesis, the formation of new blood capillaries, plays a key role in regenerative lung growth after unilateral pneumonectomy (PNX). We have reported that obesity inhibits angiogenesis. The effects of obesity on post-PNX lung vascular and alveolar regeneration remain unclear. Unilateral PNX is performed on Lep o b / o b obese mice to examine vascular and alveolar regeneration. Regenerative lung growth and expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR2 induced after PNX are inhibited in Lep o b / o b obese mice. The levels of adiponectin that exhibits pro-angiogenic and vascular protective properties increase after unilateral PNX, while the effects are attenuated in Lep o b / o b obese mice. Post-PNX regenerative lung growth and increases in the levels of VEGF and VEGFR2 are inhibited in adiponectin knockout mice. Adiponectin stimulates angiogenic activities in human lung endothelial cells (ECs), which is inhibited by decreasing the levels of transcription factor Twist1. Adiponectin agonist, AdipoRon restores post-PNX lung growth and vascular and alveolar regeneration in Lep o b / o b obese mice. These findings suggest that obesity impairs lung vascular and alveolar regeneration and adiponectin is one of the key factors to improve lung regeneration in obese people.

Growth and Biomass Yield of Grey Sedge (Lepironia articulata Retz. Domin) under Different Shoot-Cutting Intervals in a Tropical Peatland

Grey sedge (Lepironia articulata Retz. Domin) is a plant endemic to tropical peatlands and is widely used as a handicraft and biodegradable product that brings income to local farmers. However, its habitat has been decreasing due to peatland degradation, which has forced local farmers to harvest L. articulata repeatedly in the same habitat. To examine the effects of repeated shoot cutting at different time intervals on L. articulata growth and biomass yield, a mesocosm experiment was conducted from June 2019 to March 2020 in a tropical peatland in Perigi village, Ogan Ilir District, South Sumatra, Indonesia, using a randomized block design with four treatments and three replicates. The treatments were as follows: P1 (cutting every 1 month), P2 (cutting every 2 months), P3 (cutting every 3 months), and P4 (cutting at 6-months). The results showed that P1 significantly reduced monthly shoot height, shoot diameter, shoot number, dry biomass, cumulative shoot number, and cumulative dry biomass. In contrast, considering L. articulata‘s regenerative growth, the growth and cumulative biomass yield of P3 (1453.5 ± 518.4 g m−2) were as good as those of P4. These results indicate that the harvesting interval should be longer than 3 months for the sustainable use of L. articulata in tropical peatlands without damaging its regenerative ability.

Damage-induced basal epithelial cell migration modulates the spatial organization of redox signaling and sensory neuron regeneration.

Epithelial damage leads to early reactive oxygen species (ROS) signaling, which regulates sensory neuron regeneration and tissue repair. How the initial type of tissue injury influences early damage signaling and regenerative growth of sensory axons remains unclear. Previously we reported that thermal injury triggers distinct early tissue responses in larval zebrafish. Here, we found that thermal but not mechanical injury impairs sensory axon regeneration and function. Real-time imaging revealed an immediate tissue response to thermal injury characterized by the rapid Arp2/3-dependent migration of keratinocytes, which was associated with tissue scale ROS production and sustained sensory axon damage. Isotonic treatment was sufficient to limit keratinocyte movement, spatially restrict ROS production, and rescue sensory neuron function. These results suggest that early keratinocyte dynamics regulate the spatial and temporal pattern of long-term signaling in the wound microenvironment during tissue repair.

Voltage-gated calcium channels generate blastema Ca 2+ fluxes restraining zebrafish fin regenerative outgrowth.

Adult zebrafish fins regenerate to their original size regardless of damage extent, providing a tractable model of organ size and scale control. Gain-of-function of voltage-gated K + channels expressed in fibroblast-lineage blastema cells promotes excessive fin outgrowth, leading to a long-finned phenotype. Similarly, inhibition of the Ca 2+ -dependent phosphatase calcineurin during regeneration causes dramatic fin overgrowth. However, Ca 2+ fluxes and their potential origins from dynamic membrane voltages have not been explored or linked to fin size restoration. We used fibroblast-lineage GCaMP imaging of regenerating adult fins to identify dynamic and heterogeneous Ca 2+ transients in distal blastema cells. Membrane depolarization of isolated regenerating fin fibroblasts triggered Ca 2+ spikes dependent on voltage-gated Ca 2+ channel activity. Single cell transcriptomics identified the voltage-gated Ca 2+ channels cacna1c (L-type channel), cacna1ba (N-type), and cacna1g (T-type) as candidate mediators of fibroblast-lineage Ca 2+ signaling. Small molecule inhibition revealed L- and/or N-type voltage-gated Ca 2+ channels act during regenerative outgrowth to restore fins to their original scale. Strikingly, cacna1g homozygous mutant zebrafish regenerated extraordinarily long fins due to prolonged outgrowth. The regenerated fins far exceeded their original length but with otherwise normal ray skeletons. Therefore, cacna1g mutants uniquely provide a genetic loss-of-function long-finned model that decouples developmental and regenerative fin outgrowth. Live GCaMP imaging of regenerating fins showed T-type Cacna1g channels enable Ca 2+ dynamics in distal fibroblast-lineage blastemal mesenchyme during the outgrowth phase. We conclude "bioelectricity" for fin size control likely entirely reflects voltage-modulated Ca 2+ dynamics in fibroblast-lineage blastemal cells that specifically and steadily decelerates outgrowth at a rate tuned to restore the original fin size.

Long-Term Survival and Regeneration Following Transplantation of 3D-Printed Biodegradable PCL Tracheal Grafts in Large-Scale Porcine Models.

Polycaprolactone (PCL) implants in large animals show great promise for tracheal transplantation. However, the longest survival time achieved to date is only about three weeks. To meet clinical application standards, it is essential to extend the survival time and ensure the complete integration and functionality of the implant. Our study investigates the use of three-dimensional (3D)-printed, biodegradable, PCL-based tracheal grafts for large-scale porcine tracheal transplantation, assessing the feasibility and early structural integrity crucial for long-term survival experiments. A biodegradable PCL tracheal graft was fabricated using a BIOX bioprinter and transplanted into large-scale porcine models. The grafts, measuring 20 × 20 × 1.5 mm, were implanted following a 2 cm circumferential resection of the porcine trachea. The experiment design was traditionally implanted in eight porcines to replace four-ring tracheal segments, only two of which survived more than three months. Data were collected on the graft construction and clinical outcomes. The 3D-printed biosynthetic grafts replicated the native organ with high fidelity. The implantations were successful, without immediate complications. At two weeks, bronchoscopy revealed significant granulation tissue around the anastomosis, which was managed with laser ablation. The presence of neocartilage, neoglands, and partial epithelialization near the anastomosis was verified in the final pathology findings. Our study demonstrates in situ regenerative tissue growth with intact cartilage following transplantation, marked by neotissue formation on the graft's exterior. The 90-day survival milestone was achieved due to innovative surgical strategies, reinforced with strap muscle attached to the distal trachea. Further improvements in graft design and granulation tissue management are essential to optimize outcomes.

Growth patterns of caudal fin rays are informed by both external signals from the regenerating organ and remembered identity autonomous to the local tissue

Regenerating tissues must remember or interpret their spatial position, using this information to restore original size and patterning. The external skeleton of the zebrafish caudal fin is composed of 18 rays; after any portion of the fin is amputated, position-dependent regenerative growth restores each ray to its original length. We tested for transcriptional differences during regeneration of proximal versus distal tissues and identified 489 genes that differed in proximodistal expression. Thyroid hormone directs multiple aspects of ray patterning along the proximodistal axis, and we identified 364 transcripts showing a proximodistal expression pattern that was dependent on thyroid hormone context. To test what aspects of ray positional identity are directed by extrinsic environental cues versus remembered identity autonomous to the tissue, we transplanted distal portions of rays to proximal environments and evaluated regeneration within the new location. Native regenerating proximal tissue showed robust expression of scpp7, a transcript with thyroid-regulated proximal enrichment; in contrast, regenerating rays originating from transplanted distal tissue showed reduced (distal-like) expression during outgrowth. These distal-to-proximal transplants regenerated far beyond the length of the graft itself, indicating that cues from the proximal environment promoted additional growth. Nonetheless, these transplants initiated regeneration at a much slower rate compared to controls, suggesting memory of distal identity was retained by the transplanted tissue. This early growth retardation caused rays that originated from transplants to grow noticeably shorter than neighboring native rays. While several aspects of fin ray morphology (bifurcation, segment length) were found to be determined by the environment, we found that both regeneration speed and ray length are remembered autonomously by tissues, and that persist through multiple rounds of amputation and regeneration.

TET3 Contributes to Exercise-Induced Functional Axon Regeneration and Visual Restoration.

Axons have intrinsically poor regenerative capacity in the mature central nervous system (CNS), leading to permanent neurological impairments in individuals. There is growing evidence that exercise is a powerful physiological intervention that can obviously enhance cell rejuvenate capacity, but its molecular mechanisms that mediate the axonal regenerative benefits remain largely unclear. Using the eye as the CNS model, here it is first indicated that placing mice in an exercise stimulation environment induced DNA methylation patterns and transcriptomes of retinal ganglion cell, promoted axon regeneration after injury, and reversed vision loss in aged mice. These beneficial effects are dependent on the DNA demethylases TET3-mediated epigenetic effects, which increased the expression of genes associated with the regenerative growth programs, such as STAT3, Wnt5a, Klf6. Exercise training also shows with the improved mitochondrial and metabolic dysfunction in retinas and optic nerves via TET3. Collectively, these results suggested that the increased regenerative capacity induced by enhancing physical activity is mediated through epigenetic reprogramming in mouse model of optic nerve injury and in aged mouse. Understanding the molecular mechanism underlying exercise-dependent neuronal plasticity led to the identification of novel targets for ameliorating pathologies associated with etiologically diverse diseases.

RNA-sequencing reveals differential fibroblast responses to bleomycin and pneumonectomy.

Pulmonary fibrosis is characterized by pathological accumulation of scar tissue in the lung parenchyma. Many of the processes that are implicated in fibrosis, including increased extracellular matrix synthesis, also occur following pneumonectomy (PNX), but PNX instead results in regenerative compensatory growth of the lung. As fibroblasts are the major cell type responsible for extracellular matrix production, we hypothesized that comparing fibroblast responses to PNX and bleomycin (BLM) would unveil key differences in the role they play during regenerative versus fibrotic lung responses. RNA-sequencing was performed on flow-sorted fibroblasts freshly isolated from mouse lungs 14 days after BLM, PNX, or sham controls. RNA-sequencing analysis revealed highly similar biological processes to be involved in fibroblast responses to both BLM and PNX, including TGF-β1 and TNF-α. Interestingly, we observed smaller changes in gene expression after PNX than BLM at Day 14, suggesting that the fibroblast response to PNX may be muted by expression of transcripts that moderate pro-fibrotic pathways. Itpkc, encoding inositol triphosphate kinase C, was a gene uniquely up-regulated by PNX and not BLM. ITPKC overexpression in lung fibroblasts antagonized the pro-fibrotic effect of TGF-β1. RNA-sequencing analysis has identified considerable overlap in transcriptional changes between fibroblasts following PNX and those overexpressing ITPKC.

Prey species restrict limb regenerative growth in a ladybird beetle, Cheilomenes sexmaculata: allocation costs of regeneration?

ABSTRACT In aphidophagous ladybird beetles, amputation of limbs in the larval stage leads to limb regeneration in adults. Regeneration is an energetically expensive phenomenon, and altering prey species may have profound consequences on this process. Therefore, we hypothesised that the quality of prey species will impact the ability to regenerate the lost limbs in Cheilomenes sexmaculata. For this experiment, we reared the larvae of C. sexmaculata on two aphid prey species: Aphis craccivora, which is the most preferred good-quality aphid, and A. nerii, which is the least preferred, poor-quality aphid. Although regeneration occurred in both dietary regimes, the extent of regeneration was higher in the beetles fed on A. craccivora. The length of the regenerated legs was shorter than the control/unamputated beetles, and it was further reduced when the prey species was of poor-quality indicating additional utilisation of resources for tissue repair and regeneration. Regeneration delayed pupal duration, post-amputation developmental duration and relative growth rate (RGR). Poor diet negatively affected developmental durations and RGR. Our results indicate prey dependency on regeneration and highlight energetic demands of regeneration and its associated developmental allocation costs.

A report on the impact of CGF on hard and soft tissues around endo-perio lesion.

There is an increased chance of further periodontal deterioration due to severe intrabony defect. There are s different patho physiologies for perio-endo lesions, ranging from quite basic to rather complicated but to make the right diagnosis, one must be aware of various illness processes also a careful history taking, examination, and the application of specialized tests can help achieve this. Each form of endodontic-periodontal illness has a different prognosis and course of therapy and all kinds of endo-perio lesions require endodontic and periodontal treatments are necessary for primary periodontal disease with subsequent endodontic involvement and real mixed endodontic-periodontal disorders. The severity of the periodontal disease and how well the patient responds to therapy will determine how these situations turn out. Because autologous platelet concentrates are enriched with growth factors, such as concentrated growth factor (CGF), they may enhance surgical outcomes. CGF is inserted into the appropriate intrabony defect following traditional flap debridement. Following flap surgery, the tooth in question had a root canal operation. Volumetric analysis was performed on both groups before to surgery and nine months after the procedure. It has been discovered that the defect area has a much larger bone volume due to the high levels of CGF, a regenerative and reconstructive growth factor that promotes early and high bone fill.

O-GlcNAc signaling increases neuron regeneration through one-carbon metabolism in Caenorhabditis elegans.

Cellular metabolism plays an essential role in the regrowth and regeneration of a neuron following physical injury. Yet, our knowledge of the specific metabolic pathways that are beneficial to neuron regeneration remains sparse. Previously, we have shown that modulation of O-linked β-N-acetylglucosamine (O-GlcNAc) signaling, a ubiquitous post-translational modification that acts as a cellular nutrient sensor, can significantly enhance in vivo neuron regeneration. Here, we define the specific metabolic pathway by which O-GlcNAc transferase (ogt-1) loss of function mediates increased regenerative outgrowth. Performing in vivo laser axotomy and measuring subsequent regeneration of individual neurons in C. elegans, we find that glycolysis, serine synthesis pathway (SSP), one-carbon metabolism (OCM), and the downstream transsulfuration metabolic pathway (TSP) are all essential in this process. The regenerative effects of ogt-1 mutation are abrogated by genetic and/or pharmacological disruption of OCM and the SSP linking OCM to glycolysis. Testing downstream branches of this pathway, we find that enhanced regeneration is dependent only on the vitamin B12 independent shunt pathway. These results are further supported by RNA sequencing that reveals dramatic transcriptional changes by the ogt-1 mutation, in the genes involved in glycolysis, OCM, TSP, and ATP metabolism. Strikingly, the beneficial effects of the ogt-1 mutation can be recapitulated by simple metabolic supplementation of the OCM metabolite methionine in wild-type animals. Taken together, these data unearth the metabolic pathways involved in the increased regenerative capacity of a damaged neuron in ogt-1 animals and highlight the therapeutic possibilities of OCM and its related pathways in the treatment of neuronal injury.

Rejuvenation of bone volume with CGF and i-PRF in intra-osseous defects.

The risk of further periodontal breakdown increases with a deep intrabony defect. Non-surgical periodontal therapy could pose a challenge and surgical intervention is mainly required to manage the defect. Autologous platelet concentrates such as Injectable platelet rich fibrin (i-PRF) and concentrated growth factor (CGF) may improve surgical outcome due to its enrichment with growth factors. Total of 04 patients involved in this study. After conventional flap debridement of intrabony defects, CGF is placed in 2 patients and the other 2 patients received i-PRF in their respective intrabony defects. Volumetric analysis was done pre-operative and 6 months post operatively in both the groups. Bone volume is significantly increased in both CGF and i-PRF group but higher in CGF group when compared to i-PRF group has high regenerative and reconstructive growth factors which helps aids in early and high bone fill when compared to i-PRF.

Drosophila activins adapt gut size to food intake and promote regenerative growth

Rapidly renewable tissues adapt different strategies to cope with environmental insults. While tissue repair is associated with increased intestinal stem cell (ISC) proliferation and accelerated tissue turnover rates, reduced calorie intake triggers a homeostasis-breaking process causing adaptive resizing of the gut. Here we show that activins are key drivers of both adaptive and regenerative growth. Activin-β (Actβ) is produced by stem and progenitor cells in response to intestinal infections and stimulates ISC proliferation and turnover rates to promote tissue repair. Dawdle (Daw), a divergent Drosophila activin, signals through its receptor, Baboon, in progenitor cells to promote their maturation into enterocytes (ECs). Daw is dynamically regulated during starvation-refeeding cycles, where it couples nutrient intake with progenitor maturation and adaptive resizing of the gut. Our results highlight an activin-dependent mechanism coupling nutrient intake with progenitor-to-EC maturation to promote adaptive resizing of the gut and further establish activins as key regulators of adult tissue plasticity.

Innate immune and proinflammatory signals activate the Hippo pathway via a Tak1-STRIPAK-Tao axis

The Hippo pathway controls developmental, homeostatic and regenerative tissue growth, and is frequently dysregulated in various diseases. Although this pathway can be activated by innate immune/inflammatory stimuli, the underlying mechanism is not fully understood. Here, we identify a conserved signaling cascade that leads to Hippo pathway activation by innate immune/inflammatory signals. We show that Tak1, a key kinase in innate immune/inflammatory signaling, activates the Hippo pathway by inducing the lysosomal degradation of Cka, an essential subunit of the STRIPAK PP2A complex that suppresses Hippo signaling. Suppression of STRIPAK results in the activation of Hippo pathway through Tao-Hpo signaling. We further show that Tak1-mediated Hippo signaling is involved in processes ranging from cell death to phagocytosis and innate immune memory. Our findings thus reveal a molecular connection between innate immune/inflammatory signaling and the evolutionally conserved Hippo pathway, thus contributing to our understanding of infectious, inflammatory and malignant diseases.

Modern advances in spinal cord regeneration: hydrogel combined with neural stem cells.

Severe spinal cord injuries (SCI) lead to loss of functional activity of the body below the injury site, affect a person's ability to self-care and have a direct impact on performance. Due to the structural features and functional role of the spinal cord in the body, the consequences of SCI cannot be completely overcome at the expense of endogenous regenerative potential and, developing over time, lead to severe complications years after injury. Thus, the primary task of this type of injury treatment is to create artificial conditions for the regenerative growth of damaged nerve fibers through the area of the SCI. Solving this problem is possible using tissue neuroengineering involving the technology of replacing the natural tissue environment with synthetic matrices (for example, hydrogels) in combination with stem cells, in particular, neural/progenitor stem cells (NSPCs). This approach can provide maximum stimulation and support for the regenerative growth of axons of damaged neurons and their myelination. In this review, we consider the currently available options for improving the condition after SCI (use of NSC transplantation or/and replacement of the damaged area of the SCI with a matrix, specifically a hydrogel). We emphasise the expediency and effectiveness of the hydrogel matrix + NSCs complex system used for the reconstruction of spinal cord tissue after injury. Since such a complex approach (a combination of tissue engineering and cell therapy), in our opinion, allows not only to creation of conditions for supporting endogenous regeneration or mechanical reconstruction of the spinal cord, but also to strengthen endogenous regeneration, prevent the spread of the inflammatory process, and promote the restoration of lost reflex, motor and sensory functions of the injured area of spinal cord.

Modernization of the Urban Infrastructure of Ekaterinburg – Sverdlovsk in 1923–1930

Introduction. The article examines the process of formation and modernization of the urban infrastructure of Ekaterinburg – Sverdlovsk during the period of the New Economic Policy (NEP). The main mechanisms for the development of the urban economy are shown in conditions of regenerative growth of economics and a rapid increase of city’s population. The transformation of Ekaterinburg into Sverdlovsk, the administrative and political center of the Ural region, opened up opportunities to concentrate in it the local community resources and attract government funding. Using of limited market mechanisms of the NEP allowed the Sverdlovsk City Council to develop large infrastructure projects in conditions of moderate co-financing from the state. Results. Despite the large number of publications on local history, a comprehensive study of the processes of modernization of the urban infrastructure of Sverdlovsk during the NEP period was not carried out. The work analyzes the modernization of the most important sectors of urban infrastructure: electricity, transport, construction, water supply and sewerage. The abolition of command management mechanisms and the permission of private initiative in trade and small industry caused rapid growth in the city’s economy and its population. Sverdlovsk’s status as an administrative and political center of the Ural region strengthened the financial well-being of the city. The Sverdlovsk City Council received large loans from the state-controlled banking system for the development of capital construction and the development of urban infrastructure. By the end of the 1920s in Sverdlovsk, the main elements of modern urban infrastructure were created, water supply, sewerage, bus transit was built, and the construction of a tram system began. In order of regulation of economic activity and city’s property management on market conditions, a communal enterprise was created under the Sverdlovsk City Council – called Komkhoz. Conclusion. Modernization of the urban infrastructure of Sverdlovsk in 1923–1930 occurred mainly through the efforts of the local community. With the active attraction of local equity capital and loans from state-sanctioned banks, during the NEP period the city began the successful formation of a modern urban infrastructure. The course towards the development of forced industrialization of the USSR through accelerated growth of the public sector of the economy led to the gradual curtailment of private initiative on the ground in 1929–1930.

Regenerative growth is constrained by brain tumor to ensure proper patterning in Drosophila.

Some animals respond to injury by inducing new growth to regenerate the lost structures. This regenerative growth must be carefully controlled and constrained to prevent aberrant growth and to allow correct organization of the regenerating tissue. However, the factors that restrict regenerative growth have not been identified. Using a genetic ablation system in the Drosophila wing imaginal disc, we have identified one mechanism that constrains regenerative growth, impairment of which also leads to erroneous patterning of the final appendage. Regenerating discs with reduced levels of the RNA-regulator Brain tumor (Brat) exhibit enhanced regeneration, but produce adult wings with disrupted margins that are missing extensive tracts of sensory bristles. In these mutants, aberrantly high expression of the pro-growth factor Myc and its downstream targets likely contributes to this loss of cell-fate specification. Thus, Brat constrains the expression of pro-regeneration genes and ensures that the regenerating tissue forms the proper final structure.

Promoting axon regeneration by inhibiting RNA N6-methyladenosine demethylase ALKBH5.

A key limiting factor of successful axon regeneration is the intrinsic regenerative ability in both the peripheral nervous system (PNS) and central nervous system (CNS). Previous studies have identified intrinsic regenerative ability regulators that act on gene expression in injured neurons. However, it is less known whether RNA modifications play a role in this process. Here, we systematically screened the functions of all common m6A modification-related enzymes in axon regeneration and report ALKBH5, an evolutionarily conserved RNA m6A demethylase, as a regulator of axonal regeneration in rodents. In PNS, knockdown of ALKBH5 enhanced sensory axonal regeneration, whereas overexpressing ALKBH5 impaired axonal regeneration in an m6A-dependent manner. Mechanistically, ALKBH5 increased the stability of Lpin2 mRNA and thus limited regenerative growth associated lipid metabolism in dorsal root ganglion neurons. Moreover, in CNS, knockdown of ALKBH5 enhanced the survival and axonal regeneration of retinal ganglion cells after optic nerve injury. Together, our results suggest a novel mechanism regulating axon regeneration and point ALKBH5 as a potential target for promoting axon regeneration in both PNS and CNS.

Neuronal differentiation and inhibition of glial differentiation of murine neural stem cells by pHPMA hydrogel for the repair of injured spinal cord

Currently, several therapeutic methods of treating the effects of spinal cord injury (SCI) are being considered. On the one hand, transplantation of stem cells (SCs), in particular, neural stem/progenitor cells (NSPCs), is promising, as these cells have the potential to differentiate into nervous tissue cells, able to enhance endogenous regeneration and prevent the development of inflammatory processes. On the other hand, it is quite promising to replace the damaged nervous tissue with synthetic matrices, in particular hydrogels, which can create artificial conditions for the regenerative growth of injured nerve fibers through the spinal cord injury area, i.e. stimulate and support axonal regeneration and myelination. In this work, we combined both of these novel approaches by populating (injecting or rehydrating) a heteroporous pHPMA hydrogel (NeuroGel) with murine hippocampal NSPCs. Being inside the hydrogel (10 days of cultivation), NSPCs were more differentiated into neurons: 19.48% ± 1.71% (the NSPCs injection into the hydrogel) and 36.49% ± 4.20% (the hydrogel rehydration in the NSPCs suspension); in control cultures, the level of differentiation in neurons was only 2.40% ± 0.31%. Differentiation of NSPCs into glial cells, in particular into oligodendrocyte progenitor cells, was also observed – 8.89% ± 2.15% and 6.21% ± 0.80% for injection and rehydration variants, respectively; in control – 28.75% ± 2.08%. In the control NSPCs culture, there was a small number of astrocytes – 2.11% ± 0.43%. Inside the hydrogel, NSPCs differentiation in astrocytes was not observed. In vitro data showed that the hydrogel promotes the differentiation of NSPCs into neurons, and inhibits the differentiation into glial cells. And in vivo showed post-traumatic recovery of rat spinal cord tissue after injury followed by implantation of the hydrogel+NSPCs complex (approximately 7 months after SCI). The implant area was closely connected with the recipient tissue, and the recipient cells freely grew into the implant itself. Inside the implant, a formed dense neuronal network was visible. In summary, the results are primarily an experimental ground for further studies of implants based on pHPMA hydrogel with populated different origin SCs, and the data also indicate the feasibility and efficiency of using an integrated approach to reduce possible negative side effects and facilitate the rehabilitation process after a SCI.