Peripheral-blood or bone-marrow mononuclear cells for therapeutic angiogenesis?

The Lancet ◽  
2002 ◽  
Vol 360 (9350) ◽  
pp. 2083 ◽  
Author(s):  
Shoichi Inaba ◽  
Kensuke Egashira ◽  
Kimihiro Komori
The Lancet ◽  
2002 ◽  
Vol 360 (9350) ◽  
pp. 2083-2084 ◽  
Author(s):  
Tohru Minamino ◽  
Haruhiro Toko ◽  
Kaoru Tateno ◽  
Toshio Nagai ◽  
lssei Komuro

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Masafumi Takahashi ◽  
Yoshiaki Ishigatsubo ◽  
Kazuteru Fujimoto ◽  
Masaaki Miyamoto ◽  
Seiji Minota ◽  
...  

Systemic sclerosis (SSc or scleroderma) is an autoimmune connective tissue disease characterized by diffuse fibrosis, degenerative changes, and microvascular abnormalities. The vasculopathy mainly affects small arteries and capillaries and causes insufficient blood flow, which leads to clinical manifestations, such as Raynaud’s syndrome, fingertip ulcers, and gangrene. Recently, implantation of bone marrow-derived mononuclear cells (MNCs) has been successfully used for therapeutic neovascularization in Buerger’s disease that is thought to be an “autoimmune” vasculitis. The purpose of this study is to determine the efficacy of autologous MNC implantation into the ischemic digits of patients with connective tissue diseases. This study was performed as a prospective, non-randamized, and multicenter clinical trial. Thirty-four patients (19 SSc, 5 SLE, 2 CREST, 2 MCTD, 4 APS, 2 PN) who had painful ischemic digits with skin ulcers were enrolled in this study. Autologous MNCs obtained from bone marrow or peripheral blood were implanted into the ischemic digits. Ischemic pain and ulcers improved remarkably after MNC implantation. In particular, SSc patients showed dramatic improvement of these parameters (18 of 19 patients, 94.7%). In patients with other types of connective tissue diseases, pain and ulcers improved in 12 of 15 patients (80.0%). No serious adverse event was observed. These results demonstrate that implantation of autologous MNCs from bone marrow or peripheral blood into ischemic digits is feasible, safe and effective for improvement of pain and skin ulcers in patients with connective tissue diseases including SSc. Thus, larger, randomized and controlled trials for this cell therapy in patients with connective tissue diseases will be warranted.


Author(s):  
D. V. Bulgin ◽  
O. V. Andreeva

Angiogenesis is the process of new capillary formation by migration and proliferation of differentiated endothelial cells from pre-existing microvascular network. A number of angiogenic molecules and cell populations are involved in this complex of new vessel formation cascades resulting in the determination and organization of new tridimensional vascular network. The goal of therapeutic angiogenesis is to stimulate angiogenesis to improve perfusion, to deliver survival factors to sites of tissue repair, to mobilize regenerative stem cell populations, andultimately to restore form and function to the tissue. Growth factors and bone marrow as a source of bone marrow mononuclear cells represent a very interesting research fi eld for the realization of therapeutic angiogenesis in ischemic tissues. They provide a potential key component in the healing processes of ischemic injured tissues.


Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Bing Yang ◽  
Kaushik Parsha ◽  
Elton Migliati ◽  
Sean Savitz

Background: Autologous bone marrow mononuclear cells (MNCs) have been shown in multiple labs to improve stroke recovery in animal models but the mechanisms remain unclear. We assessed whether MNCs modulate macrophage-microglia responses in acute stroke. Methods: C57/BL mice were subjected to middle cerebral artery occlusion (MCAo) for 60 minutes or sham surgery. 24 hours later, they were randomized to receive saline infusion IV or 1x 10 6 autologous MNCs IV. At various time points after stroke, 1ml peripheral blood was collected and brains were harvested up to day14. Peripheral blood was labeled with anti-mouse CD45, CD115, F4/80 or Gr-1 antibodies and then assessed by flow cytometry. Microglia were isolated from brains by Optiprep gradient and stained with anti-mouse CD11b, CD45, and CD86 antibodies for evaluation by flow cytometry. For gene expression analyses by RT-PCR, microglia-macrophages were further sorted by magnetic activated-cells sorting using CD11b antibody. Results: 1) At day 2 after stroke, the percentage of CD115 + monocytes and CD115 + /Gr-1 low cells were significantly decreased in whole peripheral blood but F4/80 + macrophages were increased. MNCs increased the abundance of CD115 + /Gr-1 low cells and decreased the abundance of F4/80 + macrophages in peripheral blood compared to saline control at day 2 after stroke (n=5, p <0.05); 2)Compared to saline, MNCs significantly reduced the total number of CD11b + microglia-macrophages in the stroke-affected hemisphere at day 2 to day 6. MNCs significantly decreased the proportion of CD11b + /CD45 high among CD11b + cells at day 2 and day 4 and CD86 + cells among CD11b + cells at day 2. Among CD11b + microglia-macrophages isolated from the ipsilateral hemisphere of MNC treated mice, compared to saline treated controls, iNOS and IL-1β genes expression were down-regulated at day 2. At day 6, iNOS remained down-regulated while now IL-10, Arganase-1 and CD206 genes expression (markers for the “healing” macrophage phenotype) were up-regulated (n=3 to 5, p <0.05). Conclusions: MNCs may enhance recovery after stroke by altering monocyte trafficking and changing microglial polarization into a healing phenotype.


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