Interleukin 1ß receptor blocker (Anakinra) and regenerative stem cell therapy: two novel approaches effectively ameliorating diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) is a serious common complication of diabetes. Unfortunately, there is no satisfied treatment for those patients and more studies are in critical need to cure them. Therefore, we aimed to carry out our current research to explore the role of two novel therapeutic approaches: one a biological drug aimed to block inflammatory signaling of the IL 1beta (IL1ß) axis, namely, anakinra; the other is provision of anti-inflammatory regenerative stem cells. Wistar male rats were allocated into four groups: control group: type 2 diabetes mellitus (DM) induced by 6-week high-fat diet (HFD) followed by a single-dose streptozotocin (STZ) 35 mg/kg i.p., then rats were allocated into: DM: untreated; DM BM-MSCs: received a single dose of BM-MSCs (1 × 106 cell/rat) into rat tail vein; DM-Anak received Anak 0.5 µg/kg/day i.p. for 2 weeks. Both therapeutic approaches improved cardiac performance, fibrosis, and hypertrophy. In addition, blood glucose and insulin resistance decreased, while the antioxidant parameter, nuclear factor erythroid 2-related factor 2 (Nrf2) and interleukin 10 (IL10), and anti-inflammatory agent increased. Furthermore, there is a significant reduction in tumor necrosis factor alpha (TNFα), IL1ß, caspase1, macrophage marker CD 11b, inducible nitric oxide synthase (iNOS), and T-cell marker CD 8. Both Anak and BM-MSCs effectively ameliorated inflammatory markers and cardiac performance as compared to non-treated diabetics. Improvement is mostly due to anti-inflammatory, antioxidant, anti-apoptotic properties, and regulation of TNFα/IL1ß/caspase1 and Nrf2/IL10 pathways.

Melatonin-Pretreated Mesenchymal Stem Cells Improved Cognition in a Diabetic Murine Model.

Diabetes mellitus (DM) is a multisystem endocrine disorder affecting the brain. Mesenchymal stem cells (MSCs) pretreated with Melatonin have been shown to increase the potency of MSCs. This work aimed to compare Melatonin, stem cells, and stem cells pretreated with Melatonin on the cognitive functions and markers of synaptic plasticity in an animal model of type I diabetes mellitus (TIDM). Thirty-six rats represented the animal model; six rats for isolation of MSCs and 30 rats were divided into five groups: control, TIDM, TIDM + Melatonin, TIDM + Stem cells, and TIDM + Stem ex vivo Melatonin. Functional assessment was performed with Y-maze, forced swimming test and novel object recognition. Histological and biochemical evaluation of hippocampal Neuroligin 1, Sortilin, Brain-Derived Neurotrophic Factor (BDNF), inducible nitric oxide synthase (iNOS), toll-like receptor 2 (TLR2), Tumor necrosis factor-alpha (TNF-α), and Growth Associated Protein 43 (GAP43). The TIDM group showed a significant decrease of hippocampal Neuroligin, Sortilin, and BDNF and a significant increase in iNOS, TNF-α, TLR2, and GAP43. Melatonin or stem cells groups showed improvement compared to the diabetic group but not compared to the control group. TIDM + Stem ex vivo Melatonin group showed a significant improvement, and some values were restored to normal. Ex vivo melatonin-treated stem cells had improved spatial working and object recognition memory and depression, with positive effects on glucose homeostasis, inflammatory markers levels and synaptic plasticity markers expression.

Myelo-enhancement by astragalus membranaceus in male albino rats with chemotherapy myelo-suppression. Histological and immunohistochemical study.

BACKGROUND AND OBJECTIVES: Myelosuppression is the most common toxicity encountered in the oncology clinic today. This study was planned to investigate the possible protective and therapeutic role of the traditional Chinese Medicinal Herb; Astragalus Membranaceus (AM), on chemotherapy-induced myelosuppression. METHODS AND RESULTS: This study was carried out on thirty six adult male albino rats. They were divided into: Group I Control Group (n=6) received a vehicle of phosphate buffered saline (PBS) solution. Group II (n=12) were injected I.P. with cyclophosphamide (CY) for 3 days (gIIa n =6) and continued for one more week to receive AM orally (gIIb n=6). Group III (n=6) received CY I.P. together with AM orally for 3 days. Group IV (n=12) received AM orally for one week (gIVa n=6) and continued for extra three days receiving CY I.P. with AM orally (gIVb n=6). Blood samples were analysed for Total Leucocytic Count and Lymphocytic Count. Counting of CD34 +ve cells in bone marrow was performed by flowcytometry. Bone marrow sections were subjected to H&E stain as well as immunohistochemical staining for anti- CD20 antibody. The mean area % of cellular bone marrow regions occupied by developing haemopoietic cells, mean area of fat cells and mean number of CD20 immunopositive B lymphocytes in the bone marrow were measured by histomorphometric studies and statistically compared. AM proved to have a myelo-protective and myelo-therapeutic capacity, evidenced at both laboratory and morphological levels. CONCLUSIONS: The greatest myelo-potentiating effect of AM was achieved when supplied before and together with CY therapy.

Myelo-Enhancement by Astragalus Membranaceus in Male Albino Rats with Chemotherapy Myelo-Suppression. Histological and Immunohistochemical Study

BACKGROUND AND OBJECTIVES: Myelo-suppression is the most common toxicity encountered in the oncology clinic today. This study was planned to investigate the possible protective and therapeutic role of the traditional Chinese Medicinal Herb; Astragalus Membranaceus (AM), on chemotherapy-induced myelosuppression. METHODS AND RESULTS: This study was carried out on thirty six adult male albino rats. They were divided into: Group I Control Group (n=6) received a vehicle of phosphate buffered saline (PBS) solution. Group II (n=12) were injected I.P. with cyclophosphamide (CY) for 3 days (gIIa n =6) and continued for one more week to receive AM orally (gIIb n=6). Group III (n=6) received CY I.P. together with AM orally for 3 days. Group IV (n=12) received AM orally for one week (gIVa n=6) and continued for extra three days receiving CY I.P. with AM orally (gIVb n=6). Blood samples were analysed for Total Leucocytic Count and Lymphocytic Count. Counting of CD34 +ve cells in bone marrow was performed by flowcytometry. Bone marrow sections were subjected to H&E stain as well as immunohistochemical staining for anti- CD20 antibody. The mean area % of cellular bone marrow regions occupied by developing haemopoietic cells, mean area of fat cells and mean number of CD20 immunopositive B lymphocytes in the bone marrow were measured by histomorphometric studies and statistically compared. AM proved to have a myelo-protective and myelo-therapeutic capacity, evidenced at both laboratory and morphological levels. CONCLUSIONS: The greatest myelo-potentiating effect of AM was achieved when supplied before and together with CY therapy.

The effect of in vivo mobilization of bone marrow stem cells on the pancreas of diabetic albino rats (a histological & immunohistochemical study).

BACKGROUND AND OBJECTIVES: The rapidly increasing number of diabetic patients across the world drew the attention to develop more effective therapeutic approaches. Recent investigations on newly differentiated insulin producing cells (IPCs) revealed that they could be derived from embryonic, adult mesenchymal and hematopoietic stem cells. This work was planned to evaluate the role of StemEnhance (Aphanizomenon flos-aquae [AFA] plant extract) in mobilizing naturally occurring bone marrow stem cells as well as in improving streptozotocin-induced diabetic rats. METHODS AND RESULTS: Twenty adult male albino rats were divided into four groups namely the control, the diabetic, the positive control-StemEnhance and the diabetic-StemEnhance groups. After diabetes induction by streptozotocin (STZ), rats received StemEnhance for four weeks. The mean number of blood CD34 immunopositive cells was measured by flowcytometry and random blood sugar was measured weekly. The pancreas was removed from the sacrificed rats and processed for staining with H&E and immunohistochemical staining for CD34+ve and insulin +ve cells. CD34+ve cells increased in the blood after introduction of StemEnhance. CD34+ve cells were observed in the pancreas and the insulin producing cells in the islets of Langerhans were increased from the second to the fourth week of treatment. Blood glucose level improved but it was still higher than the control level after four weeks of StemEnhance treatment. CONCLUSIONS: This work points to the significant role of StemEnhance in stem cell mobilization and the improvement of diabetes mellitus.

The Effect of In Vivo Mobilization of Bone Marrow Stem Cells on the Pancreas of Diabetic Albino Rats (A Histological & Immunohistochemical Study)

BACKGROUND AND OBJECTIVES: The rapidly increasing number of diabetic patients across the world drew the attention to develop more effective therapeutic approaches. Recent investigations on newly differentiated insulin producing cells (IPCs) revealed that they could be derived from embryonic, adult mesenchymal and hematopoietic stem cells. This work was planned to evaluate the role of StemEnhance (Aphanizomenon flos-aquae [AFA] plant extract) in mobilizing naturally occurring bone marrow stem cells as well as in improving streptozotocin-induced diabetic rats. METHODS AND RESULTS: Twenty adult male albino rats were divided into four groups namely the control, the diabetic, the positive control-StemEnhance and the diabetic-StemEnhance groups. After diabetes induction by streptozotocin (STZ), rats received StemEnhance for four weeks. The mean number of blood CD34 immunopositive cells was measured by flowcytometry and random blood sugar was measured weekly. The pancreas was removed from the sacrificed rats and processed for staining with H&E and immunohistochemical staining for CD34+ve and insulin +ve cells. CD34+ve cells increased in the blood after introduction of StemEnhance. CD34+ve cells were observed in the pancreas and the insulin producing cells in the islets of Langerhans were increased from the second to the fourth week of treatment. Blood glucose level improved but it was still higher than the control level after four weeks of StemEnhance treatment. CONCLUSIONS: This work points to the significant role of StemEnhance in stem cell mobilization and the improvement of diabetes mellitus.

Effect of Stem Cell Therapy on Adriamycin Induced Tubulointerstitial Injury

BACKGROUND AND OBJECTIVES: It was postulated that adriamycin (ADR) induce renal tubulointerstitial injury. Clinicians are faced with a challenge in producing response in renal patients and slowing or halting the evolution towards kidney failure. The present study aimed at investigating the relation between the possible therapeutic effect of human mesenchymal stem cells (HMSCs), isolated from cord blood on tubular renal damage and their distribution by using ADR induced nephrotoxicity as a model in albino rat. METHODS AND RESULTS: Thirty three male albino rats were divided into control group, ADR group where rats were given single intraperitoneal (IP) injection of 5 mg/kg adriamycin. The rats were sacrificed 10, 20 and 30 days following confirmation of tubular injury. In stem cell therapy group, rats were injected with HMSCs following confirmation of renal injury and sacrificed 10, 20 and 30 days after HMSCs therapy. Kidney sections were exposed to histological, histochemical, immunohistochemical, morphometric and serological studies. In response to SC therapy, vacuolated cytoplasm, dark nuclei, detached epithelial lining and desquamated nuclei were noticed in few collecting tubules (CT). 10, 20 and 30 days following therapy. The mean count of CT showing desquamated nuclei and mean value of serum creatinine revealed significant difference in ADR group. The mean area% of Prussian blue+ve cells and that of CD105 +ve cells measured in subgroup S1 denoted a significant increase compared to subgroups S2 and S3. CONCLUSIONS: ADR induced tubulointerstitial damage that regressed in response to cord blood HMSC therapy.