scholarly journals ASSESMENT OF ANTI-NOCICEPTIVE ACTIONS OF ADIPOSE-DERIVED MESEMCHYMAL STEM CELLS IN EXPERIMENTAL PERIPHERAL NEUROPATHIC PAIN

2021 ◽  
Vol 29 (5) ◽  
pp. 527-534
Author(s):  
A.-M. Yerofeyeva ◽  
◽  
I. Zhavaranak ◽  
O. Antipova ◽  
N. Schastnaya ◽  
...  

Objective. To estimate an anti-nociceptive and regenerative potential of adipose-derived mesenchymal stem cells in experimental post-traumatic neuropathy in rats. Methods. Neuropathic pain was induced by axotomy technique in rat left hind paw (Wistar rats (n=113)). The respective group of subjects received ADMSCs dose of 1×10<sup>6</sup> cells/kg and 2×10<sup>6</sup> cells/kg into the site of sciatic nerve injury at 2 regimens: single (7<sup>th</sup> day post-surgery) and twice (7<sup>th</sup> and 14<sup>th</sup> day post-surgery). Nociceptive responses, as well as histological changes of sciatic nerve and perineural tissue were assessed in dynamics. Results. Sciatic nerve axotomy led to a significant increase of mechanical nociceptive sensitivity of ipsilateral hind paw by 7<sup>th</sup> day, as well as to fibrotic changes of peri- and epineural areas of damaged nerve fibers and to denervation of surrounding muscle tissue and fascia. Local administration of ADMSCs effectively abolished mechanical hyperalgesia by 14<sup>th</sup> day after first injection at all regimens tested. Among tested regimens, the most pronounced anti-nociceptive and regenerative effects were induced by single injection of ADMSCs (1×10<sup>6</sup> cells/kg). As the dose and frequency of ADMSCs administration elevated, their reparative and anti-inflammatory properties reduced. Conclusion. Obtained results testify anti-nociceptive potential of ADMSCs and feasibility of its further investigation on the experimental models of neuropathy. What this paper adds For the first time the impact of different regimen of allogenic adipose-derived mesenchymal stem cells (ADMSCs) transplantation on nociceptive sensitivity and microstructure changes of sciatic nerve in rats with peripheral neuropathy has been studied. Allogenic transplantation of mesenchymal stem cells at a dose of 1×10<sup>6</sup> cells/kg has been found out to exhibit the most powerful anti-nociceptive and regenerative effects with a single local injection confirmed by algometry and histological study.

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Shimaa Mohammad Yousof ◽  
Doaa Attia ElSayed ◽  
Amani A. El-Baz ◽  
Hanaa S. Sallam ◽  
Faten Abbas

Aims. Neuropathic pain following nerve injury does not respond well to most available pharmacological remedies. We aimed to compare the outcome of the addition of adipose-derived mesenchymal stem cells (ADMSCs) to pregabalin for neuropathic pain treatment. Methods. Adult female albino rats ( n = 100 ) were randomized to receive traumatic sciatic nerve injury or sham. Animals were then randomized to ADMSC treatment with or without pregabalin. We conducted a battery of neurobehavioral and electrophysiological to assess neuropathic pain. Following sacrifice, we evaluated the histological changes and gene expression of brain-derived neurotrophic factor (BDNF) in the sciatic nerve. Serum and sciatic nerve tissue pro- and inflammatory cytokine levels were also assessed. Results. (1) All treatments significantly improved thermal withdrawal latency, sciatic nerve conduction velocity, and proinflammatory cytokine levels in injured animals, with no significant effect of the combined treatments compared to pregabalin monotherapy ( p < 0.05 each). (2) Combined treatment significantly improved medial gastrocnemius electromyographic amplitude and sciatic function index compared to pregabalin monotherapy ( p < 0.05 each). (3) Combined treatment significantly increased the BDNF expression, decreased anti-inflammatory cytokine ( p < 0.05 each), and restored the structural nerve damage, compared to pregabalin monotherapy. Conclusions. Combined treatment is associated with greater improvement of the sciatic nerve structure and function. Further studies are warranted to study the mechanism of action of the combined treatment to improve neuropathic pain.


2019 ◽  
Vol 6 (3) ◽  
Author(s):  
V. Pyatykop ◽  
V. Kaliuzhka ◽  
O. Shchegelska ◽  
M. Markevych

Abstract EFFICACY OF FIBRIN MATRIX WITH NEUROINDUCED MESENCHYMAL STEM CELLS TRANSPLANTATION FOR RESTORATION SCIATIC NERVE FUNCTION AFTER ITS COMPLETE RUPTURE IN RATS Piatykop V., Kaliuzhka V., Shchegelska O., Markevych M. Peripheral nerves damage is a frequent pathology with significant socio-economic significance. The aim is to study the possibility of using fibrin matrices filled with neuroinduced mesenchymal stem cells (nMSC) to restore integrity of peripheral nerves. Methods. The study was carried out on 40 mongrel female rats. Sciatic nerves (SN) of all rats were intersected and then reconstituted using various methods. nMSC were obtained from rats` bone marrow and cultivated by special method. Results. Total anatomical rupture of SN without treatment led to persistent neurologic deficit (SFI = -98) in E1 group. Partial restoration of SN function increased to SFI = -37 on the 30th day in E2 (operative reconstruction) group. Partial restoration of SN function occurred after 20 days (SFI = -64) in E3 group (transplanted acellular fibrin matrix). Partial restoration of SN function started at the 3rd day, stably increased to SFI=-27 on 30th day in E4 group (transplanted fibrin matrix with nMSC). Histological evaluation showed: there were alternating portions of connective tissue with portions of nerve fibers in E2 group; in E3 group large scar was formed at the place of transplanted fibrin matrix; in E4 were found spindle-shaped and stellate cells with long processes running from one side of SN to another, cells of connective tissue and thin nerve fibers. Conclusions. It has been shown that transplantation of the fibrin matrix with nMSC was more effective for treatment of SN trauma than transplantation of cell-free fibrin matrix and close to the results of surgical reconstruction. Keywords: mesenchymal stem cells, sciatic nerve, fibrin matrix.   Резюме ЕФЕКТИВНІТЬ ТРАНСПЛАНТАЦІЇ ФІБРИНОВИХ МАТРИЦЬ ЗНЕЙРОІНДУКОВАНИМИ МЕЗЕНХІМАЛЬНИМИ  СТОВБУРОВИМИ КЛІТИНАМИДЛЯ ВІДНОВЛЕННЯ ФУНКЦІЇ СІДНИЧНОГО НЕРВУ ПІСЛЯ ЙОГО РОЗРИВУ УЩУРІВ П’ятикоп В.О., Калюжка В.Ю., Щегельська О.А., Маркевич М.А. Пошкодження периферичних нервів є частою патологією, що має значне соціально-економічне значення. Метою роботи є вивчення можливості використання фібринових матриць, заповнених нейроиндукованими мезенхімальними стовбуровими клітинами (нМСК) для відновлення цілісності периферичних нервів. Методи. Дослідження проводили на 40 беспородних щурах. Сідничні нерви (СН) всіх щурів перетинали і потім відновлювали їх цілісність різними методами. МСК отримували з кісткового мозку щурів і культивували спеціальним методом.Результати. Загальний анатомічний розрив СН без лікування призводив до стійкого неврологічного дефіциту (Sciatic functional index (SFI) = -98) у групі Е1. Часткове відновлення функції СН зросло до SFI = -37 на 30-й день у групі E2 (оперативна реконструкція). Часткове відновлення функції СН відбувалося через 20 днів (SFI = -64) в групі Е3 (трансплантований фібриновий безклітинний матрикс). Часткове відновлення функції SN починалося на 3-й день, стабільно збільшувалося до SFI=-27 на 30-й день у групі E4 (трансплантований фібриновий матрикс з нМСК). Гістологічна оцінка показала: формувались ділянки сполучної тканини з ділянками нервових волокон у групі Е2; у групі Е3 великий сполучнотканинниий рубець утворився на місці трансплантованого фібринового матриксу; в Е4 були виявлені веретеноподібні і зірчасті клітини з довгими відросткамии від однієї сторони СН до іншої, клітини сполучної тканини і тонкі нервові волокна. Висновки. Було показано, що трансплантація фібринового матриксу з нМСК була більш ефективною для лікування травми СН, ніж трансплантація безклітинної фібринової матриці та близька до результатів хірургічної реконструкції.Ключові слові: мезенхімальні стовбурові клітини, сідничний нерв, фібринова матриця.   Резюме. ЭФЕКТИВНОСТЬ ТРАНСПЛАНТАЦИИ ФИБРИНОВЫХ МАТРИЦ С НЕЙРОИНДУЦИРОВАННЫМИ МЕЗЕНХИМАЛЬНЫМИ СТВОЛОВЫМИ КЛЕТКАМИ ДЛЯ ВОССТАНОВЛЕНИЯ ФУНКЦИИ СЕДАЛИЩНОГО НЕРВА ПОСЛЕ ЕГО РАЗРЫВА У КРЫС. Пятикоп В.А., Калюжка В.Ю., Щегельская Е.А., Маркевич Н.А. Повреждение периферических нервов является частой патологией, имеющей значительное социально-экономическое значение. Цель состоит в том, чтобы изучить возможность использования фибриновых матриц, заполненных нейроиндуцированными мезенхимальными стволовыми клетками (нМСК), для восстановления целостности периферических нервов. Методы. Исследование проведено на 40 беспородных самках крыс. Седалищные нервы (СН) всех крыс пересекали и затем восстанавливали, используя различные методы. нМСК получали из костного мозга крыс и культивировали специальным способом. Результаты. Полный анатомический разрыв СН без лечения привел к стойкому неврологическому дефициту (SFI = -98) в группе Е1. Частичное восстановление функции SN увеличилось до SFI = -37 на 30-й день в группе E2 (оперативная реконструкция). Частичное восстановление функции СН произошло через 20 дней (SFI = -64) в группе E3 (трансплантированный фибриновый бесклеточный матрикс). Частичное восстановление функции СН началось на 3-й день, стабильно увеличилось до SFI = -27 на 30-й день в группе Е4 (трансплантированный фибриновый матрикс с нМСК). Гистологическая оценка показала: в группе Е2 были чередующиеся участки соединительной ткани с нервными волокнами; в группе Е3 образовался крупный рубец на месте трансплантированного фибринового матрикса; в E4 были обнаружены веретенообразные и звездчатые клетки с длинными отростками, идущими от одной стороны СН к другой, клетками соединительной ткани и тонкими нервными волокнами. Выводы. Было показано, что трансплантация фибринового матрикса с нМСК была более эффективной для лечения травмы СН, чем трансплантация бесклеточного фибринового матрикса и близка к результатам хирургической реконструкции. Ключевые слова: мезенхимальные стволовые клетки, седалищный нерв, фибриновая матрица


2020 ◽  
Vol 10 (7) ◽  
pp. 966-970
Author(s):  
Lei Zhang ◽  
Yongbin Ma ◽  
Hui Wang ◽  
Jianyi Gao ◽  
Kai Ye ◽  
...  

Peripheral nerve injure seriously endangers human health and new methods involving stem cells are currently being developed, these cells may exert their function primarily through secretory microvesicles (MVs) and various small molecules. MVs have become the key mediators of intercellular communication. In this study, MVs secreted by human embryonic stem cell-derived mesenchymal stem cells (hESC-MSC-MVs) were isolated by ultracentrifugation. A Sprague-Dawley rat model of sciatic nerve crush injury was established with 36 Sprague-Dawley rats. Efficacy evaluations including rat footprint test, the HE staining of nerve fibers and the HE staining of gastrocnemius muscle fibers were conducted two weeks after the injection of hESC-MSC-MVs through caudal vein. Results showed that hESC-MSC-MVs obviously had an effect of nerve injury repair and inhibited the denervation atrophy of gastrocnemius muscles. This implied that hESC-MSC-MVs with great regenerative properties might offer an alternative therapeutic option for treating peripheral neuropathy.


2021 ◽  
Vol 8 (3) ◽  
Author(s):  
Siyawash Xaki ◽  
Afshin Fathi ◽  
Mehdi Ariana ◽  
Hamid Reza Aghayan ◽  
Babak Arjmand ◽  
...  

Background: Peripheral nerve injuries remain a great challenge for microsurgery despite the significant progress in recent decades. The current gold standard is autogenous nerve grafting with a success rate as low as 50% in long gaps. Current studies have focused on finding alternative methods for bridging nerve defects. Previous data have demonstrated the role of human amniotic membrane in stimulating neural regeneration. On the other hand, adipose-derived mesenchymal stem cells can differentiate into all three germ layers and could support nerve repair. The purpose of this study was to compare the role of the human amniotic membrane with and without adipose tissue stem cells in sciatic nerve injury with gap in rats. Objectives: We aimed to evaluate the effectiveness of the human amniotic membrane with and without adipose-derived mesenchymal stem cells in sciatic nerve injury with gap in rats. Methods: Twenty-four male Wistar rats in four random groups were used in our study. In the first group, the nerve gap was repaired using the inverse resected nerve segment (Control group), the second group was repaired with a human amniotic membrane (AM group), the third group was repaired with an amnion sheet with seeded adipose-derived mesenchymal stem cells (AM/ADMSCs group), and the last group was not repaired, and both stumps were sutured to muscles. Results: All the animals underwent the procedures and survived without complication. The sciatic function index and hot plate test results were significantly improved in the AM and AM/ADMSCs groups compared to the Control group (as a gold standard of care) (P>0.05). Based on histopathology findings, regenerative nerve fibers were seen in the implanted area of both AM and AM/ADMSCs groups; however, nerve fibers were surrounded by significant fibrosis (scar formation) in the AM/ADMSCs group. The axon count in the Control group was significantly higher than both experimental groups (P < 0.01). Conclusions: Our study showed the role of amniotic membrane in the promotion of nerve regeneration in sciatic nerve injury with a gap, but adding adipose-derived mesenchymal stem cells not only has no extra benefits, but also causes more tissue scar.


2018 ◽  
Vol 55 (4) ◽  
pp. 691-695
Author(s):  
Tudor Sorin Pop ◽  
Anca Maria Pop ◽  
Alina Dia Trambitas Miron ◽  
Klara Brinzaniuc ◽  
Simona Gurzu ◽  
...  

The use of collagen scaffolds and stem cells for obtaining a tissue-engineering complex has been an important concept in promoting repair and regeneration of the bone tissue. Such units represent important steps in the development of an ideal scaffold-cell complex that would sustain new bone apposition. The aim of our study was to perform a histologic evaluation of the healing of critical-sized bone defects, using a biologic collagen scaffold with adipose-derived mesenchymal stem cells, in comparison to negative controls created in the adjacent bone. We used 16 Wistar rats and according to the study design 2 calvarial bone defects were created in each animal, one was filled with collagen seeded with adipose-derived stem cells and the other one was considered negative control. During the following month, at weekly intervals, the animals were euthanized and the specimens from bone defects were histologically evaluated. The results showed that these scaffolds were highly biocompatible as only moderate inflammation no rejection reactions were observed. Furthermore, the first signs of osseous healing appeared after two weeks accompanied by angiogenesis. Collagen scaffolds seeded with adipose-derived mesenchymal stem cells can be considered a promising treatment option in bone regeneration of large defects.


Catalysts ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 62
Author(s):  
Won-Yong Jeon ◽  
Seyoung Mun ◽  
Wei Beng Ng ◽  
Keunsoo Kang ◽  
Kyudong Han ◽  
...  

Enzymatic biofuel cells (EBFCs) have excellent potential as components in bioelectronic devices, especially as active biointerfaces to regulate stem cell behavior for regenerative medicine applications. However, it remains unclear to what extent EBFC-generated electrical stimulation can regulate the functional behavior of human adipose-derived mesenchymal stem cells (hAD-MSCs) at the morphological and gene expression levels. Herein, we investigated the effect of EBFC-generated electrical stimulation on hAD-MSC cell morphology and gene expression using next-generation RNA sequencing. We tested three different electrical currents, 127 ± 9, 248 ± 15, and 598 ± 75 nA/cm2, in mesenchymal stem cells. We performed transcriptome profiling to analyze the impact of EBFC-derived electrical current on gene expression using next generation sequencing (NGS). We also observed changes in cytoskeleton arrangement and analyzed gene expression that depends on the electrical stimulation. The electrical stimulation of EBFC changes cell morphology through cytoskeleton re-arrangement. In particular, the results of whole transcriptome NGS showed that specific gene clusters were up- or down-regulated depending on the magnitude of applied electrical current of EBFC. In conclusion, this study demonstrates that EBFC-generated electrical stimulation can influence the morphological and gene expression properties of stem cells; such capabilities can be useful for regenerative medicine applications such as bioelectronic devices.


Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 339
Author(s):  
Tobias Grossner ◽  
Uwe Haberkorn ◽  
Tobias Gotterbarm

First-line analgetic medication used in the field of musculoskeletal degenerative diseases, like Nonsteroidal anti-inflammatory drugs (NSAIDs), reduces pain and prostaglandin synthesis, whereby peptic ulcers are a severe adverse effect. Therefore, proton pump inhibitors (PPI) are frequently used as a concomitant medication to reduce this risk. However, the impact of NSAIDs or metamizole, in combination with PPIs, on bone metabolism is still unclear. Therefore, human mesenchymal stem cells (hMSCs) were cultured in monolayer cultures in 10 different groups for 21 days. New bone formation was induced as follows: Group 1 negative control group, group 2 osteogenic differentiation media (OSM), group 3 OSM with pantoprazole (PAN), group 4 OSM with ibuprofen (IBU), group 5 OSM with diclofenac (DIC), group 6 OSM with metamizole (MET), group 7 OSM with ibuprofen and pantoprazole (IBU + PAN), group 8 OSM with diclofenac and pantoprazole (DIC + PAN), group 9 OSM with metamizole and pantoprazole (MET + PAN) and group 10 OSM with diclofenac, metamizole and pantoprazole (DIC + MET + PAN). Hydroxyapatite content was evaluated using high-sensitive radioactive 99mTc-HDP labeling. Within this study, no evidence was found that the common analgetic medication, using NSAIDs alone or in combination with pantoprazole and/or metamizole, has any negative impact on the osteogenic differentiation of mesenchymal stem cells in vitro. To the contrary, the statistical results indicate that pantoprazole alone (group 3 (PAN) (p = 0.016)) or diclofenac alone (group 5 (DIC) (p = 0.008)) enhances the deposition of minerals by hMSCS in vitro. There is an ongoing discussion between clinicians in the field of orthopaedics and traumatology as to whether post-surgical (pain) medication has a negative impact on bone healing. This is the first hMSC in vitro study that investigates the effects of pain medication in combination with PPIs on bone metabolism. Our in vitro data indicates that the assumed negative impact on bone metabolism is subsidiary. These findings substantiate the thesis that, in clinical medicine, the patient can receive every pain medication needed, whether or not in combination with PPIs, without any negative effects for the osteo-regenerative potential.


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