Review: cellularity in bone marrow autografts for bone and fracture healing.

The use of autografts, as primary cell and tissue source, is the current gold standard approach to treat critical size bone defects and nonunion defects. The unique mixture of the autografts, containing bony compartments and bone marrow (BM), delivers promising results. Although BM mesenchymal stromal cells (BM-MSCs) still represent a major target for various healing approaches in current preclinical research and respective clinical trials, their occurrence in the human BM is typically low. In vitro expansion of this cell type is regulatory challenging as well as time and cost intensive. Compared with marginal percentages of resident BM-MSCs in BM, BM mononuclear cells (BM-MNCs) contained in BM aspirates, concentrates, and bone autografts represent a readily available abundant cell source, applicable within hours during surgical procedures without the need for time-consuming and regulatory challenging cell expansion. This benefit is one reason why autografting has become a clinical standard procedure. However, the exact anatomy and cellularity of BM-MNCs in humans, which is strongly correlated to their unique mode of action and wide application range remains to be elucidated. The aim of this review was to present an overview of the current knowledge on these specific cell types found in human BM, emphasize the contribution of BM-MNCs in bone healing, highlight donor site dependence, and discuss limitations in the current isolation and subsequent characterization procedures. Hereby, the most recent and relevant examples of human BM-MNC cell characterization, flow cytometric analyses, and findings are summarized, with a strong focus on bone therapy.

A multilayered electrospun graft as vascular access for hemodialysis.

Despite medical achievements, the number of patients with end-stage kidney disease keeps steadily raising, thereby entailing a high number of surgical and interventional procedures to establish and maintain arteriovenous vascular access for hemodialysis. Due to vascular disease, aneurysms or infection, the preferred access-an autogenous arteriovenous fistula-is not always available and appropriate. Moreover, when replacing small diameter blood vessels, synthetic vascular grafts possess well-known disadvantages. A continuous multilayered gradient electrospinning was used to produce vascular grafts made of collagen type I nanofibers on luminal and adventitial graft side, and poly-ɛ-caprolactone as medial layer. Therefore, a custom-made electrospinner with robust environmental control was developed. The morphology of electrospun grafts was characterized by scanning electron microscopy and measurement of mechanical properties. Human microvascular endothelial cells were cultured in the graft under static culture conditions and compared to cultures obtained from dynamic continuous flow bioreactors. Immunofluorescent analysis showed that endothelial cells form a continuous luminal layer and functional characteristics were confirmed by uptake of acetylated low-density-lipoprotein. Incorporation of vancomycin and gentamicin to the medial graft layer allowed antimicrobial inhibition without exhibiting an adverse impact on cell viability. Most striking a physiological hemocompatibility was achieved for the multilayered grafts.

[Immunological markers of disease activity in the course of 2-CDA treatment of multiple sclerosis]. / Immunologiczne markery aktywnosci choroby w przebiegu leczenia kladrybina stwardnienia rozsianego.

52 clinically definite multiple sclerosis (MS) patients were treated with subcutaneous injection of 5 mg 2-CDA in 5 consecutive days. The injection courses were repeated 6 times in one month interval. The MRI pattern and immunological markers were studied in serum and CSF before and after 6 months of treatment. The obtained results suggest that treatment with 2-CDA has not any significant effect on humoral immunological events in multiple sclerosis, what is in contrast to some normalization of cellular immunopathological processes.

[Myelin basic protein stimulation index of CD 2 cells in the course of steroid treatment]. / Wskaznik stymulacji bialkiem zasadowym komórek CD 2 w czasie leczenia steroidami stwardnienia rozsianego.

Myelin basic protein CD 2 lymphocyte stimulation index calculated as the proportion of percentage of myelin basic protein stimulated CD 2 lymphocytes to unstimulated CD 2 lymphocytes was evaluated in a group of 23 multiple sclerosis patients in the course of prednisone or methylprednisolone treatment. After both treatments a decrease of myelin basic protein CD 2 lymphocyte stimulation index was observed, statistically significant after methyloprednisolone medication.

[Urine free light chains kappa in multiple sclerosis]. / Wolne lancuchy kappa w moczu w stwardnieniu rozsianym.

The evaluation of free light chains kappa in urine was performed in 77 cases of multiple sclerosis, including 52 patients before and after treatment with 2 CDA and in 25 patients before and after therapy with high doses of prednisone. The high variations in the level of free kappa chains indicate a limited diagnostic value, and only for cases with very high level. We have found effect of 2 CDA therapy in chronic progressive MS group on free kappa light chain value. A significant effect of prednisone treatment was observed in early onset cases of multiple sclerosis and in cases with clinical improvement after therapy. In conclusion, the study suggests that urinary free light chains level may be considered as one of markers for monitoring of the effect of therapy on the activity of the immunological processes in multiple sclerosis.

[Results of one-year treatment of multiple sclerosis with azathioprine compared with the therapy using small doses of Encorton]. / Wyniki rocznego leczenia stwardnienia rozsianego azatiopryna w porównaniu z terapia malymi dawkami Encortonu.

A group of 21 patients with clinically confirmed multiple sclerosis were treated for one year with azathioprine, Germed, in daily doses of 50 or 75 mg depending on body weight. After two months the treatment was stopped for one month. The control group received prednisone (Encorton, Polfa) 5 or 10 mg daily. The drugs were given in wafers in powdered form. The double blind method was used. After one year the comparison of both groups failed to show any significant differences, and the reduction in the indices of exacerbations and stabilization of the process evaluated by Kurtzke's scale were nearly identical. However, this might have been due to the fact that nearly one-third of the patients dropped out from both groups. During the treatment with azathioprine no significant differences were noted in the surface phenotypes of peripheral blood mononuclear cells.

[Late results of alternate treatment of multiple sclerosis with encorton and decaris]. / Odlegle wyniki leczenia naprzemien-nego stwardnienia rozsianego Encortonem i Decarisem.

A group of 18 patients with clinically definite multiple sclerosis were subjected to alternate treatment with Prednisone (Polfa) and Decaris (Richter). The results were compared with those in a control group of 18 cases treated exclusively with Prednisone during exacerbations of the disease. The results indicate that the alternate treatment has not any significant effect on the course of multiple sclerosis, evaluated by the Kurtzke disability scale. The alternate treatment with a mild immunosuppression Encorton and immunomodulation-Decaris (Levamisole) leads to significant decrease of relapses in comparison with the period before the treatment, as well as in comparison with the control group treated exclusively with Encorton in case of exacerbations.

[Late results of the treatment of the chronic progressive form of multiple sclerosis by intensive immunosuppression]. / Odlegle wyniki leczenia postaci przewlekle postepujacej stwardnienia rozsianego intensywna immunosupresja.

A group of 16 patients with secondary chronic progression of multiple sclerosis treated by short-lasting intensive immunosuppression (cyclophosphamide with ACTH) by the programme of Hausser et al (4) was compared with a clinically similar group of 16 patients treated exclusively with intramuscular ACTH. During 2 years of observation of the patients it was observed that short-lasting intensive immunosuppression induced with simultaneous administration of cyclophosphamide and ACTH had no beneficial effect on the slowly progressing form of multiple sclerosis. The observation leads to the conclusion that cyclophosphamide therapy should not be used in view of absence of favourable effect on the course of multiple sclerosis and the risk of increased frequency of malignant neoplasms which cannot be ruled out in this method.

[Early results of the treatment of chronic progressive forms of multiple sclerosis with cyclophosphamide and ACTH]. / Wczesne wyniki leczenia postaci przewlekle postepujacych stwardnienia rozsianego cyklofosfamidem i ACTH.

A group of 16 patients with chronic-progressing type of multiple sclerosis treated by intense immunosuppression (cyclophosphamide and ACTH) were followed-up for one year after completion of therapy. The results were compared with the observation of a control group of 16 patients with a similar type of multiple sclerosis. The choice of the type of therapy was done at random, and the results were assessed by a doctor who ignored the type of therapy used. In only a part of the observed cases stabilization of the disease process was observed, in a greater number in the cases treated with cyclophosphamide and ACTH than in the those treated with ACTH alone. However, the duration of follow-up is regarded as too short for reaching final conclusions regarding the effect of therapy on the course of this type of multiple sclerosis.

[Effect of alternating treatment of multiple sclerosis with encorton and levamisole on IgG synthesis within the cerebrospinal fluid spaces]. / Wplyw leczenia naprzemiennego Encortonem i levamisolem chorych na stwardnienie rozsiane na synteze IgG wewnatrz przestrzeni plynowych.

A group of 16 patients with clinically certain multiple sclerosis with a remitting course were subjected to alternating treatment with medium doses of prednisone (Encorton, Polfa) and Decaris (Richter). The cerebrospinal fluid and plasma were studied before the beginning of the treatment and after one course of alternating treatment, determining the levels of IgG and albumins, and the IgG index which is an indicator of IgG synthesis within the cerebrospinal fluid spaces. It was observed that this treatment led to a reduction of IgG synthesis but the effect of the treatment was less pronounced than that of large doses of prednisone found in the previous study.

[Early results of alternating treatment of multiple sclerosis with immunosuppressive and immunomodulating drugs]. / Wczesne wyniki leczenia naprzemiennego SM lekami immunosupresyjnymi i immunomodulacyjnymi.

A group of 18 patients with clinically certain diagnosis of multiple sclerosis were treated alternate with prednisone and Decaris (levamisole). The results were compared with those in a control group of 18 cases with similar initial clinical parameters treated exclusively with prednisone during exacerbations of the disease. Alternating treatment with the mild immunosuppressant, prednisone, and with the immunomodulating drug Decaris caused a statistically significant reduction in the number of exacerbations of multiple sclerosis, however, the effect of this treatment on the natural history of the disease could not have been established in view of the short period of follow-up.

[Late results of the treatment of multiple sclerosis with large doses of Enkorton]. / Odlegle wyniki leczenia stwardnienia rozsianego duzymi dawkami Enkortonu.

A group of MS patients treated with large doses of Prednisone (3960 mg over a period of 54 days with initial dose 200 mg per day) was observed during 4 years after the therapy and the results were compared with the control group treated with medium doses of Prednisone (initial dose 60 mg). The difference between two therapeutic groups estimated according to Kurtzke disability scale is statistically not significant. We cannot also conclude, that the large doses of Prednisone decrease the relapse rate. However it should be stressed that in patients treated with megadoses of Prednisone the secondary chronic progressive course of MS, more rarely developed than in cases treated with medium doses.