Among some orthopedic conditions that have mostly been the target of research with ortho-biologics and regenerative medicine, it is known that the conventional treatment approach for degenerative conditions such as Knee Osteoarthritis (KOA) and Degenerative Disc Disease (DDD) focuses on alleviating symptoms through various measures, including physical therapy, weight reduction, and the use of medications to control pain and inflammation. Although current conventional therapies provide symptomatic relief, their impact on the cartilage or disc is limited. Additionally, surgical procedures such as discectomies and arthroplasties have limitations and risks. The above highlights the need to continue researching new therapies for KOA and DDD. Specifically, regenerative therapy based on ortho-biologicals can complement traditional management and has been shown in clinical studies to relieve pain, improve functionality and contribute to quality of life. The administration of ortho-biologicals, specifically from mesenchymal stromal cells (MSCs), has been shown to have a favorable impact on the process of joint and disc degeneration, given their immunomodulatory effects, as well as their effects on tissue growth, formation of collagen and differentiation into chondrocytes. In particular, studies suggest that WJ-MSC therapies are safe and well tolerated, with the potential to relieve pain and improve knee and spine functionality. These cells act in various ways, such as migration towards damaged cartilage, adaptation to their hypoxic environment, promoting the survival and differentiation of endogenous MSCs, synthesis and protection of the cartilage extracellular matrix, and exhibiting anti-inflammatory and immunomodulatory properties. It is intended to share the experience of a clinical and research center treatment with WJ-MSCs, which were delivered locally (into the knee joint and intervertebral disc) in patients with chronic degenerative orthopedic conditions. Methodology. Two retrospective cohorts were analyzed according to the effects following therapy based on WJ-MSC in KOA and DDD patients. Ethical approvals were obtained by an independent ethics committee (CEI-0435-11-2022 and CEI-0324-07-2022). Informed consent forms were signed by patients. Clinical outcomes were measured by the Short-Form12 questionnaire, Visual-Analog-Scale (VAS), and Western-Ontario-McMaster-Index (WOMAC) for KOA patients and Oswestry-DisabilityIndex (ODI) for DDD patients. KOA patients were treated with a single dose of 40x106 WJ-MSC per target knee (MSC were delivered by intra-articular route), and DDD patients were treated with 10x106 WJ-MSC per target intervertebral spine disc (MSC were delivered by intradiscally and facetally route). Previously, the allogeneic WJ-MSCs were expanded in a culture medium supplemented with 10% human platelet lysate (hPL) up to passage 7. Cell marker expression and in vitro differentiation to mesodermal lineage were verified, as well as microbiological tests. Findings. During 2022, 39 KOA patients started follow-up, of whom 26 (67%) answered the questionnaires at 6 months. There was an improvement according to pain assessment at 6 months post-therapy with an average 1.5-point reduction (↓32%) and according to pain, stiffness, and functionality assessment it was demonstrated an improvement in total WOMAC with an average reduction of 12.5 points (↓36%) in patients who had a baseline score of ≥10%. In the meanwhile, during the same period, 32 DDD patients were treated for thoracolumbar back pain and started follow-up, of whom 29 (91%) answered the questionnaires at 3 months, 30 (94%) answered at 6 months, and 22 (69%) at 12 months post-therapy. There was an improvement according to pain assessment at 6 months with an average reduction of 2.3 points (↓37%), which was maintained up to 12 months post-therapy and according to disability assessment, it was demonstrated an improvement at 6 months post-therapy with an average ODI score reduction of 9.8 points (↓29%), which was maintained until 12 months post-therapy. No adverse events were noted neither in KOA nor DDD-treated patients. Conclusion and significance. Despite the evolving nature of the evidence, the study´s findings contribute to our understanding of the therapeutic benefits of WJ-MSC in KOA and DDD-diagnosed patients, who sought treatment for failure of conservative therapy and for pain and functional limitation. The improvements evidenced involve changes in the patient's quality of life. There were no serious adverse events reported, demonstrating that these therapies are safe.

Shoulder pain syndrome is a multifaceted condition that requires a comprehensive approach for effective management. This approach should encompass both the conventional orthopedic perspective and regenerative medicine strategies. The direct and indirect costs associated with the management of shoulder pain in primary care can be substantial, including expenses related to sick leave, medication, absenteeism from work and sports, sleep disturbances, financial burden, and delayed functional return to sports practice, among other consequences. Shoulder injuries, particularly those caused by overuse such as rotator cuff tendinopathy (RCT), impingement, labrum injuries, and bursitis, can significantly impact the quality of life of athletes and the wider population. Furthermore, even after arthroscopic surgery, re-tears can occur, leading to ongoing shoulder pain and loss of function. Managing these injuries solely through arthroscopic repair and physical therapy can be challenging in orthopedics due to issues such as poor healing, adhesion formation, and fatty tissue accumulation. The above justifies the need for research and innovation in the development of ortho-regenerative therapies that contribute, in a complementary manner to conventional orthopedic management, to the reduction of pain and functional limitation. Mesenchymal stromal cells (MSCs) are a variety of ortho-biologicals that have demonstrated considerable potential in promoting tendon remodeling and fibrocartilage formation, leading to enhanced biomechanical strength in the tendon. MSCs are characterized by their remarkable proliferation capacity, potent paracrine action, and pluripotency for the differentiation into various cell types. Moreover, the extracellular vesicles originating from MSCs can facilitate collagen production, reduce inflammation, and minimize adhesion formation by transporting regulatory proteins and microRNAs. Consequently, MSC-based therapy shows great promise as a therapeutic strategy for the healing of rotator cuff. Despite the significant surgical advancements to address rotator cuff tears, the effective connection between tendon tissue and bone remains a persistent challenge. However, MSCs offer a glimmer of hope, as they have demonstrated remarkable paracrine, anti-inflammatory, and angiogenic benefits. The MSC-based therapy, which entails growth factors and specific scaffolds, aims to enhance the biomechanical strength of the rotator cuff and promote fibrocartilage formation. While the studies have shown great promise, more research is necessary to evaluate the long-term safety and efficacy of the therapy in shoulder and elbow injuries, including clinical trials and observational studies. For this reason, we are delighted to share the experience of a clinical and research center that has treated patients with shoulder overuse injuries (SOI) such as RCT, impingement syndromes, labrum injuries, and bursitis using Wharton Jelly Derived-Mesenchymal Stromal Cells (WJ-MSCs). These MSCs were delivered locally, both into the glenohumeral joint and by intratendinous injections. Methodology. One retrospective cohort was analyzed according to the effects following therapy based on WJ-MSCsin SOI patients. Ethical approval was obtained by an institutional review board (IRB). Patients signed an informed consent form. SOI patients were treated with a single dose of 70x106 WJ-MSCs per target shoulder (MSCs were delivered 20x106by intraarticular and 50x106 by intratendinous injections) by an ultrasound-guided procedure. Previously, the allogeneic WJ-MSCs were expanded in a culture medium supplemented with 10% human platelet lysate (hPL) up to passage 7. Cell marker expression and in vitro differentiation to mesodermal lineage and microbiological tests were verified. Clinical outcomes were measured by the Short-Form12 questionnaire, Visual-Analog-Scale (VAS), and Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire at baseline (pre-therapy time), followed by 3-, 6- and 12-month measurements. Following previous literature, a responder to therapy was defined as a patient with a reduction of at least 2 points or more in the VAS score and a reduction of 10 points or more in the DASH score at the last available follow-up to baseline (pretherapy scores). Findings. From November 2021 to May 2023, 88 patients were treated at the institution and met the eligibility criteria for therapy, of which all responded to the 6-month follow-ups, and 25 (28.41%) completed the questionnaires at 12-month follow-ups. The mean age was 52.36 years old (SD 13.85). The mean body mass index (BMI) was 26.92 (SD 4.30). 84% (n= 74) were men. The most frequent country of origin was the USA (n= 68, 77%). 56% (n= 49) of patients had both shoulders treated, 20% (n= 18) received WJ-MSC in the left shoulder only and 25% (n= 21) in the right shoulder only. 47/88 patients (53.41%) responded favorably to therapy at 6 months, and 18/25 (72%) responded to therapy at 12 months. The 6-month VAS was significantly reduced compared to baseline (median baseline VAS= 5, IQR 2.25, median 6m VAS= 2, IQR 4, p< 0,001 Wilcoxon W test, p= 0,018 Shapiro-Wilk assumption-normality test), as was the 12-month VAS (median baseline VAS= 5, IQR 2.25, median 12m VAS= 2, IQR 3, p< 0,001 Wilcoxon W test, p= 0,042 Shapiro-Wilk assumptionnormality test). The 6-month DASH was significantly reduced compared to baseline (median baseline DASH= 31.25, IQR 24.99, median 6m DASH= 13.33, IQR 20.21, p< 0,001 Wilcoxon W test, p< 0,001 Shapiro-Wilk assumption-normality test), as was the 12-month DASH (median baseline DASH= 31.25, IQR 24.99, median 12m DASH= 11.67, IQR 18.34, p< 0,001 Wilcoxon W test, p= 0,011 Shapiro-Wilk assumption-normality test). The 6-month SF-12 Physical score was significantly increased compared to baseline (median baseline SF12-physical= 57.14, IQR 35.72, median 6m SF12-physical= 64.29, IQR 35.71, p <0,001 Wilcoxon W test, p= 0,047 Shapiro-Wilk assumptionnormality test), as did the 12-month SF-12 Physical score (mean baseline SF12-physical= 53.40, SD 21.50, mean 12m SF12- physical= 70.78, SD 21.06, p= 0,008 t-paired test, p= 0,064 Shapiro-Wilk assumption-normality test) and the 6-month SF12 Mental score (median baseline SF12-mental= 61.90, IQR 38.09, median 6m SF12-mental= 76.19, IQR 40.48, p <0,001 Wilcoxon W test, p= 0,011 Shapiro-Wilk assumption-normality test). No adverse events were noted.

Shoulder pain syndrome is a multifaceted condition that requires a comprehensive approach for effective management. This approach should encompass both the conventional orthopedic perspective and regenerative medicine strategies. The direct and indirect costs associated with the management of shoulder pain in primary care can be substantial, including expenses related to sick leave, medication, absenteeism from work and sports, sleep disturbances, financial burden, and delayed functional return to sports practice, among other consequences. Shoulder injuries, particularly those caused by overuse such as rotator cuff tendinopathy (RCT), impingement, labrum injuries, and bursitis, can significantly impact the quality of life of athletes and the wider population. Furthermore, even after arthroscopic surgery, re-tears can occur, leading to ongoing shoulder pain and loss of function. Managing these injuries solely through arthroscopic repair and physical therapy can be challenging in orthopedics due to issues such as poor healing, adhesion formation, and fatty tissue accumulation. The above justifies the need for research and innovation in the development of ortho-regenerative therapies that contribute, in a complementary manner to conventional orthopedic management, to the reduction of pain and functional limitation. Mesenchymal stromal cells (MSCs) are a variety of ortho-biologicals that have demonstrated considerable potential in promoting tendon remodeling and fibrocartilage formation, leading to enhanced biomechanical strength in the tendon. MSCs are characterized by their remarkable proliferation capacity, potent paracrine action, and pluripotency for the differentiation into various cell types. Moreover, the extracellular vesicles originating from MSCs can facilitate collagen production, reduce inflammation, and minimize adhesion formation by transporting regulatory proteins and microRNAs. Consequently, MSC-based therapy shows great promise as a therapeutic strategy for the healing of rotator cuff. Despite the significant surgical advancements to address rotator cuff tears, the effective connection between tendon tissue and bone remains a persistent challenge. However, MSCs offer a glimmer of hope, as they have demonstrated remarkable paracrine, anti-inflammatory, and angiogenic benefits. The MSC-based therapy, which entails growth factors and specific scaffolds, aims to enhance the biomechanical strength of the rotator cuff and promote fibrocartilage formation. While the studies have shown great promise, more research is necessary to evaluate the long-term safety and efficacy of the therapy in shoulder and elbow injuries, including clinical trials and observational studies. For this reason, we are delighted to share the experience of a clinical and research center that has treated patients with shoulder overuse injuries (SOI) such as RCT, impingement syndromes, labrum injuries, and bursitis using Wharton Jelly Derived-Mesenchymal Stromal Cells (WJ-MSC). These MSCs were delivered locally, both into the glenohumeral joint and by intratendinous injections. Methodology. One retrospective cohort was analyzed according to the effects following therapy based on WJ-MSC in SOI patients. Ethical approval was obtained by an institutional review board (IRB). Patients signed an informed consent form. SOI patients were treated with a single dose of 70x106 WJ-MSC per target shoulder (MSCs were delivered 20x106 by intraarticular and 50x106 by intratendinous injections) by an ultrasound-guided procedure. Previously, the allogeneic WJ-MSCs were expanded in a culture medium supplemented with 10% human platelet lysate (hPL) up to passage 7. Cell marker expression and in vitro differentiation to mesodermal lineage and microbiological tests were verified. Clinical outcomes were measured by the Short-Form12 questionnaire, Visual-Analog-Scale (VAS), and Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire at baseline (pre-therapy time), followed by 3-, 6- and 12-month measurements. Following previous literature, a responder to therapy was defined as a patient with a reduction of at least 2 points or more in the VAS score and a reduction of 10 points or more in the DASH score at the last available follow-up to baseline (pretherapy scores). Findings. From November 2021 to May 2023, 88 patients were treated at the institution and met the eligibility criteria for therapy, of which all responded to the 6-month follow-ups, and 25 (28.41%) completed the questionnaires at 12-month follow-ups. The mean age was 52.36 years old (SD 13.85). The mean body mass index (BMI) was 26.92 (SD 4.30). 84% (n= 74) were men. The most frequent country of origin was the USA (n= 68, 77%). 56% (n= 49) of patients had both shoulders treated, 20% (n= 18) received WJ-MSC in the left shoulder only and 25% (n= 21) in the right shoulder only. 47/88 patients (53.41%) responded favorably to therapy at 6 months, and 18/25 (72%) responded to therapy at 12 months. The 6-month VAS was significantly reduced compared to baseline (median baseline VAS= 5, IQR 2.25, median 6m VAS= 2, IQR 4, p< 0,001 Wilcoxon W test, p= 0,018 Shapiro-Wilk assumption-normality test), as was the 12-month VAS (median baseline VAS= 5, IQR 2.25, median 12m VAS= 2, IQR 3, p< 0,001 Wilcoxon W test, p= 0,042 Shapiro-Wilk assumptionnormality test). The 6-month DASH was significantly reduced compared to baseline (median baseline DASH= 31.25, IQR 24.99, median 6m DASH= 13.33, IQR 20.21, p< 0,001 Wilcoxon W test, p< 0,001 Shapiro-Wilk assumption-normality test), as was the 12-month DASH (median baseline DASH= 31.25, IQR 24.99, median 12m DASH= 11.67, IQR 18.34, p< 0,001 Wilcoxon W test, p= 0,011 Shapiro-Wilk assumption-normality test). The 6-month SF-12 Physical score was significantly increased compared to baseline (median baseline SF12-physical= 57.14, IQR 35.72, median 6m SF12-physical= 64.29, IQR 35.71, p <0,001 Wilcoxon W test, p= 0,047 Shapiro-Wilk assumptionnormality test), as did the 12-month SF-12 Physical score (mean baseline SF12-physical= 53.40, SD 21.50, mean 12m SF12- physical= 70.78, SD 21.06, p= 0,008 t-paired test, p= 0,064 Shapiro-Wilk assumption-normality test) and the 6-month SF12 Mental score (median baseline SF12-mental= 61.90, IQR 38.09, median 6m SF12-mental= 76.19, IQR 40.48, p <0,001 Wilcoxon W test, p= 0,011 Shapiro-Wilk assumption-normality test). No adverse events were noted. Conclusion and significance. This study´s findings contribute to our understanding of the therapeutic benefits of WJ-MSC in SOI-diagnosed patients, who sought treatment for failure of conservative therapy and pain and functional limitation. The improvements evidenced involve changes in the patient's quality of life. There were no serious adverse events reported, demonstrating that this therapy is safe.

The general designation, “stem cell” encompasses many distinct cell types. Commonl, the modifiers, “embryonic,” and “adult” are used to distinguish stem cells by the developmental stage of the animal from which they come, but these terms are becoming insufficient as new research has discovered how to turn fully differentiated adult cells back into embryonic stem cells and, conversely, adult stem cells, more correctly termed “somatic” stem cells meaning categories based on their biologic properties - pluripotent stem cells and multipotent stem cells. Their sources, characteristics, differentiation and therapeutic applications are discussed.

From the body, are found in the fetus, placenta, umbilical cord blood and infants.² Therefore, this review will sort stem cells into two Stem cells have the ability to differentiate into specific cell types. The two defining characteristics of a stem cell are perpetual self-renewal and the ability to differentiate into a specialized adult cell type. There are two major classes of stem cells: pluripotent that can become any cell in the adult body, and multipotent that are restricted to becoming a more limited population of cells. Cell sources, characteristics, differentiation and therapeutic applications are discussed. Stem cells have great potential in tissue regeneration and repair but much still needs to be learned about their biology, manipulation and safety before their full therapeutic potential can be achieved.

Stem cells have the ability to build every tissue in the human body, hence have great potential for future therapeutic uses in tissue regeneration and repair. In order for cells to fall under the definition of “stem cells,” they must display two essential characteristics. First, stem cells must have the ability of unlimited self-renewal to produce progeny exactly the same as the originating cell. This trait is also true of cancer cells that divide in an uncontrolled manner whereas stem cell division is highly regulated. Therefore, it is important to note the additional requirement for stem cells; they must be able to give rise to a specialized cell type that becomes part of the healthy animal

Two schools teach spinal anesthesia, one prefers the lateral decubitus position and the other the sitting position. The vast majority of anesthesiologists worldwide use routinely the hyperbaric solution of bupivacaine for almost all types of surgery, mainly performed in a sitting position. There is renewed interest in understanding spinal anesthesia about puncture position, the various solutions used, and the position of the operating table during the surgical procedure. Understanding the vertebral column, of the anterior and posterior roots, allows the different puncture positions and the hyperbaric, isobaric, and hypobaric solutions to offer better quality of these techniques and will be shown in this article. The application of the three solutions in different puncture positions, and the position of the surgical table during the procedure, will be shown in seven items in 14 tables, and 6 figures, for the complete understanding of spinal anesthesia. The possibility of performing hemispinal anesthesia (unilateral and posterior), and the possibility of performing completely sensory spinal anesthesia without any degree of motor block are discussed. The explanations in this article with the different puncture positions and the three local anesthetic solutions are applied both in the lumbar region and in the thoracic region.

Significant R&D investment is currently being made in the design of cost-effective devices for the manufacture of red blood cells (RBCs) from hematopoietic stem cells. Recent technological advances open perspectives for the for-profit manufacture of homologous transfusion products for alloimmunized patients, at production costs less than 1,500 euros/cRBC unit in realistic scale facilities. Stem cell lines from scarce phenotypes of universal donors will gain substantial economic value as basic assets of this new bio-industry. This paper addresses a number of issues related to this predictable consequence of the development of an RBC industry. The main strands of case law and legal literature related to cell line patents are reviewed and their applicability to putative RBC manufacturing is discussed. I examine the various conceivable patterns of compensation for stem cell donors, from full-market compensation to full-free (i.e., uncompensated) donation, and discuss their respective relevance for the collection of suitable cell lines and for the development of the industry.

Purpose: EGFR-targeted monoclonal antibodies (mAbs) provide clinical benefit in some patients with H&N squamous cell carcinoma (HNSCC), but others progress with minimal response. Missense mutations in the EGFR ectodomain (ECD) can be acquired under mAb therapy by mimicking the effect of large deletions on receptor untethering and activation. Little is known about the contribution of EGFR ECD mutations to EGFR activation and anti-EGFR response in HNSCC. Methods: We selected patient-derived HNSCC cells (UM-SCC-1) for resistance to mAb Cetuximab (CTX) by repeated, stepwise exposure to mimic what may occur clinically and identified two concurrent EGFR ECD mutations (UM-SCC-1R). We examined the competence of the mutants to bind EGF ligand or CTX. We assessed the potential impact of the mutations through visual analysis of space-filling models of the native sidechains in the original structures vs. their respective side-chain mutations. We performed CRISPR in combination with site-directed mutagenesis to test for the effect of the mutants on ligandindependent EGFR activation and sorting. We determined the effects on receptor internalization, endocytosis, downstream signaling, and radiation sensitivity. Results: UM-SCC-1R cells carried two non-synonymous missense mutations (G33S and N56K) mapping to domain I in or near the EGF binding pocket of the EGFR ECD. Structural modeling predicted that these mutants restrict the adoption of a tethered, inactive EGFR conformation while not permitting association of EGFR with the EGF ligand or CTX. Binding studies confirmed that the mutant, untethered receptor displayed a reduced affinity for both EGF and CTX but demonstrated sustained activation and presence at the cell surface with diminished internalization and sorting for endosomal degradation. Single and double-mutant models demonstrated that the G33S mutant is dominant over the N56K mutant in its effect on EGFR activation and EGF binding. CTX-resistant UM-SCC-1R cells demonstrated cross-resistance to mAb Panitumuab but, paradoxically, remained sensitive to the reversible receptor tyrosine kinase inhibitor Erlotinib. Conclusions: HNSCC cells can select for EGFR ECD mutations under EGFR mAb exposure that converge to trap the receptor in an open, constitutively activated state. These mutants impede the receptor’s competence to bind mAbs and EGF ligand and alter its endosomal trafficking, possibly explaining certain cases of clinical mAb and radiation resistance.

Fertility preservation is an emerging field in medicine that enables men, women, and children to maintain reproductive health when it is threatened by gonadotoxic treatment or no oncologic malignancies that can impair spermatogenesis and ovogenesis. Established methods include sperm cryopreservation or experimental testicular tissue cryopreservation for males, and oocyte cryopreservation or ovarian tissue cryopreservation for females. Fertility preservation treatments must be addressed through a multidisciplinary approach that involves gynecologists, urologists, oncologists, paediatricians, and professionals in the field of medically assisted reproduction.
In this denantality ERA a significant gaps in knowledge about age-related fertility decline, and egg cryopreservation conditions and its complications. It is crucial to impart to these women a better knowledge about fertility especially on the number of high-quality retrieved mature oocytes and live birth rates depend on women's age. 

Fertility preservation is an emerging field in medicine that enables men, women, and children to maintain reproductive health when it is threatened by gonadotoxic treatment or no oncologic malignancies that can impair spermatogenesis and ovogenesis. Established methods include sperm cryopreservation or experimental testicular tissue cryopreservation for males, and oocyte cryopreservation or ovarian tissue cryopreservation for females. Fertility preservation treatments must be addressed through a multidisciplinary approach that involves gynecologists, urologists, oncologists, paediatricians, and professionals in the field of medically assisted reproduction.

In this denantality ERA a significant gaps in knowledge about age-related fertility decline, and egg cryopreservation conditions and its complications. It is crucial to impart to these women a better knowledge about fertility especially on the number of high-quality retrieved mature oocytes and live birth rates depend on women's age. 

Introduction & Statement of the problem: Low back pain is one of the most frequent pains we see in our daily practice. It can have different etiologies and disc degeneration is one of the main ones leading to discogenic pain. The use of mesenchymal stem cells (MCSs) has increasingly scoped within the field of regenerative medicine and in recent years they have begun to be implanted in degenerative lumbar spinal discs with promising results. The evidence is still low grade of recommendation. We have gathered an n of 20 patients who went through this treatment with the aim of improving their pain, functionality and slowing down the catabolic and degenerative disc cascade or if possible regenerating partially or totally the disc. We developed a work protocol and want to show our experience and contribute with our results to the scientific community. Methodology: Based on clinical and imaging diagnosis we carried out a rigorous selection of patients following inclusion and exclusion criterias. We scheduled the procedure in the surgical room between March and December 2023. Under neuroleptoanesthesia, with strict asepsis and antisepsis measures, we performed an aspiration of 80mL of bone marrow (BMA) from the iliac crest. With 4 syringes of 20mL and propelling the embolus appropriately we extracted BMA. Subsequently, this material was centrifuged at 2400RPM/min for 10 min to produce a 30mL bone marrow concentrate (BMAC). From this amount, we precisely extracted the buffy coat and plasma with 10ml syringes and a 50/8 needle obtaining a total amount between 13 to 16mL. Guided by fluoroscopy, we injected 1,5 to 2mL of this concentrate rich in stem cells (BMSCs) into the pulposus nucleus of each degenerated lumbar intervertebral disc with a Pfirrmann grade between I and IV, regardless of Modic grade (1, 2 or 3). After the implant, the patients continued to be assessed in three main parameters: a) reduction of pain using the Owestry index at 3, 6 and 12 months b) functionality evaluated in kinesiology and using the SF 36 scale at 3, 6 and 12 months c) Lumbosacral MRI without contrast between 10 to 12 months post implant. Results: In our n of 20 patients we saw improvements in at least two of the 3 proposed objectives within a year of the treatment. 70% (n=14) improved their pain and functionality after 3 months. 15% (n=3) achieved improvement in their pain and functionality at 6 months. The remaining 15% did not improve after 3, 6 or 12 months. Only 2 patients have reached 10 months of follow-up and only in one we have observed minimal intradiscal changes, which might show encouraging results.

Conclusion: In our experience, mesenchymal stem cells extracted from BMAC and applied into degenerative lumbar intervertebral discs in selected patients with discogenic pain show promising results, generating improvement in the pain and functionality of the patients. 85% showed improvement in pain and functionality at 6 months. We showed that all patients who improved their functionality also improved their pain at 3 and 6 months. Signs of intradiscal rehydration on MRI is a parameter that we cannot yet evaluate since our patients do not have the described sufficient follow-up time to observe changes in them (10 to 18 months). We may conclude given the above results, that the well known immunomodulating effect of MCSs (growth factors, proangiogenic, antiapoptotic, chemoattraction, others) are seen in clinical outcome (reduction of pain and improvement of functionality) long before any changes and signs of rehydration in MRI are yet observed.

Introduction & Statement of the problem: Low back pain is one of the most frequent pains we see in our daily practice. It can have different etiologies and disc degeneration is one of the main ones leading to discogenic pain. The use of mesenchymal stem cells (MCSs) has increasingly scoped within the field of regenerative medicine and in recent years they have begun to be implanted in degenerative lumbar spinal discs with promising results. The evidence is still low grade of recommendation. We have gathered an n of 20 patients who went through this treatment with the aim of improving their pain, functionality and slowing down the catabolic and degenerative disc cascade or if possible regenerating partially or totally the disc. We developed a work protocol and want to show our experience and contribute with our results to the scientific community. Methodology: Based on clinical and imaging diagnosis we carried out a rigorous selection of patients following inclusion and exclusion criterias. We scheduled the procedure in the surgical room between March and December 2023. Under neuroleptoanesthesia, with strict asepsis and antisepsis measures, we performed an aspiration of 80mL of bone marrow (BMA) from the iliac crest. With 4 syringes of 20mL and propelling the embolus appropriately we extracted BMA. Subsequently, this material was centrifuged at 2400RPM/min for 10 min to produce a 30mL bone marrow concentrate (BMAC). From this amount, we precisely extracted the buffy coat and plasma with 10ml syringes and a 50/8 needle obtaining a total amount between 13 to 16mL. Guided by fluoroscopy, we injected 1,5 to 2mL of this concentrate rich in stem cells (BMSCs) into the pulposus nucleus of each degenerated lumbar intervertebral disc with a Pfirrmann grade between I and IV, regardless of Modic grade (1, 2 or 3). After the implant, the patients continued to be assessed in three main parameters: a) reduction of pain using the Owestry index at 3, 6 and 12 months b) functionality evaluated in kinesiology and using the SF 36 scale at 3, 6 and 12 months c) Lumbosacral MRI without contrast between 10 to 12 months post implant. Results: In our n of 20 patients we saw improvements in at least two of the 3 proposed objectives within a year of the treatment. 70% (n=14) improved their pain and functionality after 3 months. 15% (n=3) achieved improvement in their pain and functionality at 6 months. The remaining 15% did not improve after 3, 6 or 12 months. Only 2 patients have reached 10 months of follow-up and only in one we have observed minimal intradiscal changes, which might show encouraging results.

Conclusion: In our experience, mesenchymal stem cells extracted from BMAC and applied into degenerative lumbar intervertebral discs in selected patients with discogenic pain show promising results, generating improvement in the pain and functionality of the patients. 85% showed improvement in pain and functionality at 6 months. We showed that all patients who improved their functionality also improved their pain at 3 and 6 months. Signs of intradiscal rehydration on MRI is a parameter that we cannot yet evaluate since our patients do not have the described sufficient follow-up time to observe changes in them (10 to 18 months). We may conclude given the above results, that the well known immunomodulating effect of MCSs (growth factors, proangiogenic, antiapoptotic, chemoattraction, others) are seen in clinical outcome (reduction of pain and improvement of functionality) long before any changes and signs of rehydration in MRI are yet observed.

Induced pluripotent stem cells (iPSCs) were first generated by Yamanaka in 2006, revolutionizing research by overcoming limitations imposed by the use of embryonic stem cells. In terms of the conservation of endangered species, iPSC technology presents itself as a viable alternative for the manipulation of target genetics without compromising specimens. Although iPSCs have been successfully generated for various species, their application in nonmammalian species, particularly avian species, requires further in-depth investigation to cover the diversity of wild species at risk and their different protocol requirements. This study aims to provide an overview of the workflow for iPSC induction, comparing well-established protocols in humans and mice with the limited information available for avian species. In addition to the review, the use of lipid nanoparticles LNP4 for inducing pluripotent stem cells in avian and human cells will be discussed.Gene delivery via LNP4 is non-integrative, providing greater biosafety and better performance compared to methods using cationic lipids. It promotes increased delivery of DNA into the cell nucleus, higher cell viability, and exhibits lower immunogenicity compared to other cell transfection methods. Here, we discuss the somatic cell sources to be reprogrammed, genetic factors, delivery methods, enhancers, a brief history of achievements in avian iPSC derivation, the main approaches for iPSC characterization, laboratory results regarding transfection using LNP4 in nonmammalian origin cells (Feather follicle Cells – FFCs – derived from Gallus gallus and Anodorhynchus hyacinthinus) and human origin cells (spontaneously immortalized keratinocytes - HaCaT) and the future perspectives and challenges for the field. By examining the current protocols and state-of-the-art techniques employed in iPSC generation, we seek to contribute to the development of efficient and species-specific iPSC methodologies for at-risk avian species. The advancement of iPSC technology holds great promise for achieving in vitro germline competency and, consequently, addressing reproductive challenges in endangered species, providing valuable tools for basic research, bird genetic preservation and rescue, and the establishment of cryobanks for future conservation efforts.

The increasing burden of musculoskeletal disorders combined with the high utilization of opiates, NSAIDs and the relatively limited ability of traditional approaches to satisfactorily address many of the conditions that causes osteoarticular pain has spurred an increased interest in alternative treatments such as regenerative medicine therapies. Osteoarticular pain is a critical health, social, and economic issue in modern societies. Evidence is growing to support the use of orthobiologic injection treatments. Regenerative injection-based therapy has established itself as a therapeutic option for the management of osteoarthritis pain for most orthopedic conditions using platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), bone marrow aspirate (BMA) and mesenchymal stem cell from fat (biofat). This conference will show the results of this therapies in a sample of Brazilian patients with low back pain involving the muscle-ligament-facet-discal  complex, and other orthopedic degenerative conditions and osteoarthritis of joints.The increasing burden of musculoskeletal disorders combined with the high utilization of opiates, NSAIDs and the relatively limited ability of traditional approaches to satisfactorily address many of the conditions that causes osteoarticular pain has spurred an increased interest in alternative treatments such as regenerative medicine therapies. Osteoarticular pain is a critical health, social, and economic issue in modern societies. Evidence is growing to support the use of orthobiologic injection treatments. Regenerative injection-based therapy has established itself as a therapeutic option for the management of osteoarthritis pain for most orthopedic conditions using platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), bone marrow aspirate (BMA) and mesenchymal stem cell from fat (biofat). This conference will show the results of this therapies in a sample of Brazilian patients with low back pain involving the muscle-ligament-facet-discal  complex, and other orthopedic degenerative conditions and osteoarthritis of joints.

Chronic diseases confer tissue and organ damage that reduce quality of life and are widely refractory to therapy. Degenerative diseases are strongly associated with chronic inflammation in patients who are candidates for regenerative medicine treatments. Although stem cells hold promise for treating degenerative diseases, the regenerative capacity of stem cells is influenced by regulatory networks guided by local immune responses to tissue damage. Recent research has turned to how cellular and signaling components of the local stromal microenvironment (the 'soil' to the stem cells' seed), such as local inflammatory reactions, contribute to successful tissue regeneration. For this reason, it is important to consider that all measures cabale of decreasing the degree of inflammation in the body are appropriate for the preparation of the patient: sleep, gut microbiome,    environmental toxins, hormone balance, electromagnetic fields and other illness conditions, to pose the patient in a balanced position for the regenerative procedures. Application of “preparing the soil” concepts to regenerative medicine strengthens prospects for developing cell-based therapies or for promotion of endogenous repair