Stem cell (SC) transplantation has shown potential as a therapeutic approach for premature ovarian failure (POF). Despite this, no quantitative analysis has been conducted on the efficacy of SC therapy for POF in humans. To address this gap, the present study conducted a meta-analysis to evaluate the effectiveness of the transplantation of SC in improving ovarian function among POF patients. A systematic review in this regard by searching PubMed, ScienceDirect, clinicalTrial.gov, and Cochrane\'s library databases was conducted to identify relevant studies, while associated reviews were also considered. The extracted data included parameters such as estradiol (E2), follicle-stimulating hormone (FSH), follicle count (FC), ovarian weight (OW), number of pregnancies, and live birth. As per the combined effect taking the last follow-up time, the level of FSH and AMH for the SC group was lower than these were at the baseline as (SMD: 1.58, 95% CI: 0.76 to 3.92, P-value: 0.185 > 0.05, I2: 94.03%) and (SMD: 1.34, 95% CI: 0.77 to 1.92, P-value: 0.001 < 0.05, I2: 0%) respectively. While the means of E2 and OW for the SC group was higher than these were at the baseline as (SMD: -0.47, 95% CI: -0.73 to -0.21, P-value: 0.001 < 0.01, I2: 38.23%) and (SMD: -1.18, 95% CI: -2.62 to 0.26, P-value: 0.108 > 0.05, I2: 76.68%) respectively. The overall effect size measured with proportion of pregnancy and live birth at a 5% level of significance expected SC transplantation results were as (combined proportion: 0.09, 95% CI: 0.03 to 0.15, P-value: 0.002 < 0.05, I2: 46.29%) and (SMD: 0.09, 95% CI: 0.03 to 0.15, P-value: 0.003 < 0.05, I2: 1.76%) respectively. Based on the fixed-effects model, the estimated average log odds ratio of Follicles count was 1.0234 (95% CI: 0.1252 to 1.9216). Therefore, the average outcome differed significantly from zero (P-value: 0.0255 < 0.05) due to SC transplantation. These results suggest that using SCs to restore ovarian function may be viable for treating POF. However, larger and better-quality investigations would need to be conducted in the future due to the heterogeneity of the examined studies.

OBJECTIVE: The objective of this study was to develop and evaluate the feasibility and safety of a novel transaxial surgical approach for the delivery of human induced pluripotent stem cell-derived dopaminergic neuroprogenitor cells (DANPCs) into the putamen nucleus using nonhuman primates and surgical techniques and tools relevant to human clinical translation.
METHODS: Nine immunosuppressed, unlesioned adult cynomolgus macaques (4 females, 5 males) received intraputaminal injections of vehicle or DANPCs (0.9 × 105 to 1.1 × 105 cells/µL) under real-time intraoperative MRI guidance. The infusates were combined with 1-mM gadoteridol (for intraoperative MRI visualization) and delivered via two tracks per hemisphere (ventral and dorsal) using a transaxial approach. The total volumes of infusion were 25 µL and 50 µL for the right and left putamen, respectively (infusion rate 2.5 µL/min). Animals were evaluated with a battery of clinical and behavioral outcome measures and euthanized 7 or 30 days postsurgery; full necropsies were performed by a board-certified veterinary pathologist. Brain tissues were collected and processed for immunohistochemistry, including against the human-specific marker STEM121.
RESULTS: The optimized surgical technique and tools produced successful targeting of the putamen via the transaxial approach. Intraoperative MR images confirmed on-target intraputaminal injections in all animals. All animals survived to scheduled termination without clinical evidence of neurological deficits. The first 4 animals to undergo surgery had mild brain swelling noted at the end of surgery, of which 3 had transient reduced vision; administration of mannitol therapy and reduced intravenous fluid during the surgical procedure addressed these complications. Immunostaining against STEM121 confirmed the presence of grafted cells along the injection track within the targeted putamen area of DANPC-treated animals. All adverse histological findings were limited in scope and consistent with surgical manipulation, injection procedure, and postsurgical inflammatory response to the mechanical disruption caused by the cannula insertion.
CONCLUSIONS: The delivery system, injection procedure, and DANPCs were well tolerated in all animals. Prevention of mild brain swelling by mannitol dosing and reduction of intravenous fluids during surgery allowed visual effects to be avoided. The results of the study established that this novel transaxial approach can be used to correctly and safely target cell injections to the postcommissural putamen and support clinical investigation.

Lower motor neuron (LMN) damage results in denervation of the associated muscle targets and is a significant yet under-appreciated component of spinal cord injury (SCI). Denervated muscle undergoes a progressive degeneration and fibro-fatty infiltration that eventually renders the muscle non-viable unless reinnervated within a limited time window. The distal nerve deprived of axons also undergoes degeneration and fibrosis making it less receptive to axons. In this review, we describe the LMN injury associated with SCI and its clinical consequences. The process of degeneration of the muscle and nerve is broken down into the primary components of the neuromuscular circuit and reviewed, including the nerve and Schwann cells, the neuromuscular junction, and the muscle. Finally, we discuss three promising strategies to reverse denervation atrophy. These include providing surrogate axons from local sources; introducing stem cell-derived spinal motor neurons into the nerve to provide the missing axons; and finally, instituting a training program of high-energy electrical stimulation to directly rehabilitate these muscles. Successful interventions for denervation atrophy would significantly expand reconstructive options for cervical SCI and could be transformative for the predominantly LMN injuries of the conus medullaris and cauda equina.

Retinal organoids are three-dimensional (3D) microscopic tissues that are induced and differentiated from stem cells or progenitor cells in vitro and have a highly similar structure to the retina. With the optimization and development of 3D retinal culture system and the improvement of induced differentiation technology, retinal organoids have broad application prospects in retinal development, regenerative medicine, biomaterial evaluation, disease mechanism investigation, and drug screening. In this review we summarize recent development of retinal organoids and their applications in ophthalmic regenerative medicine. In particular, we highlight the promise and challenges in the use of retinal organoids in disease modeling and drug discovery.

Development and regeneration occur by a process of genetically encoded spatiotemporally dynamic cellular interactions. The use of cell transplantation between animals to track cell fate and to induce mismatches in the genetic, spatial, or temporal properties of donor and host cells is a powerful means of examining the nature of these interactions. Organisms such as chick and amphibians have made crucial contributions to our understanding of development and regeneration, respectively, in large part because of their amenability to transplantation. The power of these models, however, has been limited by low genetic tractability. Likewise, the major genetic model organisms have lower amenability to transplantation. The zebrafish is a major genetic model for development and regeneration, and while cell transplantation is common in zebrafish, it is generally limited to the transfer of undifferentiated cells at the early blastula and gastrula stages of development. In this article, we present a simple and robust method that extends the zebrafish transplantation window to any embryonic or larval stage between at least 1 and 7 days post fertilization. The precision of this approach allows for the transplantation of as little as one cell with near-perfect spatial and temporal resolution in both donor and host animals. While we highlight here the transplantation of embryonic and larval neurons for the study of nerve development and regeneration, respectively, this approach is applicable to a wide range of progenitor and differentiated cell types and research questions.

Recognizing the limitations of current therapies for Addison\'s disease, novel treatments that replicate dynamic physiologic corticosteroid secretion, under control of ACTH, are required. The aim of these experiments was to evaluate the feasibility of adrenocortical cell transplantation (ACT) in a large animal model, adapting methods successfully used for intracutaneous pancreatic islet cell transplantation, using a fully biodegradable temporizing matrix. Autologous porcine ACT was undertaken by bilateral adrenalectomy, cell isolation, culture, and intracutaneous injection into a skin site preprepared using a biodegradable temporizing matrix (BTM) foam. Hydrocortisone support was provided during adrenocortical cell engraftment and weaned as tolerated. Blood adrenocortical hormone concentrations were monitored, and the transplant site was examined at endpoint. Outcome measures included cellular histochemistry, systemic hormone production, and hydrocortisone independence. Transplanted adrenocortical cells showed a capability to survive and proliferate within the intracutaneous site and an ability to self-organize into discrete tissue organoids with features of the normal adrenal histologic architecture. Interpretation of systemic hormone levels was confounded by the identification of accessory adrenals and regenerative cortical tissue within the adrenal bed postmortem. Corticosteroids were unable to be completely ceased. ACT in a large animal model has not previously been attempted, yet it is an important step toward clinical translation. These results demonstrate rhe potential for ACT based on the development of adrenal organoids at the BTM site. However, the inability to achieve clinically relevant systemic hormone production suggests insufficient function, likely attributable to insufficient cells through delivered dose and subsequent proliferation.

BACKGROUND: Numerous chemical reprogramming techniques have been reported, rendering them applicable to regenerative medicine research. The aim of our study was to evaluate the therapeutic potential of human CLiP derived from clinical specimens transplanted into a nonalcoholic steatohepatitis (NASH) mouse model of liver fibrosis.
METHODS: We successfully generated chemically induced liver progenitor (CLiP), which exhibited progenitor-like characteristics, through stimulation with low-molecular-weight compounds. We elucidated their cell differentiation ability and therapeutic effects. However, the therapeutic efficacy of human CLiP generated from clinical samples on liver fibrosis, such as liver cirrhosis, remains unproven.
RESULTS: Following a 4 week period, transplanted human CLiP in the NASH model differentiated into mature hepatocytes and demonstrated suppressive effects on liver injury markers (i.e., aspartate transaminase and alanine transaminase). Although genes related to inflammation and fat deposition did not change in the human CLiP transplantation group, liver fibrosis-related factors (Acta2 and Col1A1) showed suppressive effects on gene expression following transplantation, with approximately a 60% reduction in collagen fibers. Importantly, human CLiP could be efficiently induced from hepatocytes isolated from the cirrhotic liver, underscoring the feasibility of using autologous hepatocytes to produce human CLiP.
CONCLUSIONS: Our findings demonstrate the effectiveness of human CLiP transplantation as a viable cellular therapy for liver fibrosis, including NASH liver. These results hold promise for the development of liver antifibrosis therapy utilizing human CLiP within the field of liver regenerative medicine.

Spinal cord injury (SCI) is a sensory-motor injury. Today, combined treatments such as cell therapy along with drug therapy and their interactions are of interest. Morphine is an opioid drug used to relieve intolerable pain. This study aims to evaluate the impact of an antinociceptive dose of morphine (with minimal tolerance/dependence but effective pain relief) on cell therapy in SCI. The antinociceptive dose of morphine was determined in rats with SCI through the Hargreaves and naloxone-induced morphine withdrawal tests. The rats were then allocated to 5 groups: laminectomy, SCI, SCI + Morphine, SCI + cell therapy, SCI + Morphine + cell therapy. The antinociceptive dose (5 mg/kg) was administered on days 1, 4, 10, and 13 (i.p.) post-SCI. On day 7, Neural-like stem cells derived from adipose tissue were transplanted intraspinally into the injured animals, and they were monitored for 12 weeks. The outcomes were assessed using the BBB test, somatosensory evoked potential (SSEP), and histology. The BBB test indicated that morphine significantly hindered functional recovery post-cell transplantation compared to animals receiving only cell therapy (p < 0.05). In the SSEP test, the analysis of amplitude and latency of waves did not reveal a significant difference (p > 0.05). The histological results showed that cell therapy reduced the cavity size post-SCI, while morphine had no significant impact on it. Morphine at the antinociceptive dose significantly impairs motor recovery despite cell therapy. Nonetheless, there was no significant difference between groups in terms of sensory pathway outcomes.

Nerve injury can not only lead to sensory and motor dysfunction, but also be complicated with neuropathic pain (NPP), which brings great psychosomatic injury to patients. At present, there is no effective treatment for NPP. Based on the functional characteristics of cell transplantation in nerve regeneration and injury repair, cell therapy has been used in the exploratory treatment of NPP and has become a promising treatment of NPP. In this article, we discuss the current mainstream cell types for the treatment of NPP, including Schwann cells, olfactory ensheathing cells, neural stem cells and mesenchymal stem cells in the treatment of NPP. These bioactive cells transplanted into the host have pharmacological properties of decreasing pain threshold and relieving NPP by exerting nutritional support, neuroprotection, immune regulation, promoting axonal regeneration, and remyelination. Cell transplantation can also change the microenvironment around the nerve injury, which is conducive to the survival of neurons. It can effectively relieve pain by repairing the injured nerve and rebuilding the nerve function. At present, some preclinical and clinical studies have shown that some encouraging results have been achieved in NPP treatment based on cell transplantation. Therefore, we discussed the feasible strategy of cell transplantation as a treatment of NPP and the problems and challenges that need to be solved in the current application of cell transplantation in NPP therapy.

Glial cells, a type of non-neuronal cell found in the central nervous system (CNS), play a critical role in maintaining homeostasis and regulating CNS functions. Recent advancements in technology have paved the way for new therapeutic strategies in the fight against glaucoma. While intraocular pressure (IOP) is the most well-known modifiable risk factor, a significant number of glaucoma patients have normal IOP levels. Because glaucoma is a complex, multifactorial disease influenced by various factors that contribute to its onset and progression, it is imperative that we consider factors beyond IOP to effectively prevent or slow down the disease\'s advancement. In the realm of CNS neurodegenerative diseases, glial cells have emerged as key players due to their pivotal roles in initiating and hastening disease progression. The inhibition of dysregulated glial function holds the potential to protect neurons and restore brain function. Consequently, glial cells represent an enticing therapeutic candidate for glaucoma, even though the majority of glaucoma research has historically concentrated solely on retinal ganglion cells (RGCs). In addition to the neuroprotection of RGCs, the proper regulation of glial cell function can also facilitate structural and functional recovery in the retina. In this review, we offer an overview of recent advancements in understanding the non-cell-autonomous mechanisms underlying the pathogenesis of glaucoma. Furthermore, state-of-the-art technologies have opened up possibilities for regenerating the optic nerve, which was previously believed to be incapable of regeneration. We will also delve into the potential roles of glial cells in the regeneration of the optic nerve and the restoration of visual function.