Hypoxic conditioned medium derived from bone marrow mesenchymal stromal cells protects against ischemic stroke in rats

2018 ◽  
Vol 234 (2) ◽  
pp. 1354-1368 ◽  
Author(s):  
Run-Hao Jiang ◽  
Chen-Jiang Wu ◽  
Xiao-Quan Xu ◽  
Shan-Shan Lu ◽  
Qing-Quan Zu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Ischemic Stroke ◽  
Conditioned Medium ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells

scholarly journals Conditioned Medium of Bone Marrow-Derived Mesenchymal Stromal Cells as a Therapeutic Approach to Neuropathic Pain: A Preclinical Evaluation

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Kelly Barbosa Gama ◽  
Dourivaldo Silva Santos ◽  
Afrânio Ferreira Evangelista ◽  
Daniela Nascimento Silva ◽  
Adriano Costa de Alcântara ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Conditioned Medium ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Therapeutic Potential ◽  
Antinociceptive Effect ◽  
Live Cells ◽  
Reference Drug

Neuropathic pain is a type of chronic pain caused by injury or dysfunction of the nervous system, without effective therapeutic approaches. Mesenchymal stromal cells (MSCs), through their paracrine action, have great potential in the treatment of this syndrome. In the present study, the therapeutic potential of MSC-derived conditioned medium (CM) was investigated in a mouse model of neuropathic pain induced by partial sciatic nerve ligation (PSL). PSL mice were treated by endovenous route with bone marrow-derived MSCs (1 × 106), CM, or vehicle. Gabapentin was the reference drug. Twelve hours after administration, neuropathic mice treated with CM exhibited an antinociceptive effect that was maintained throughout the evaluation period. MSCs also induced nonreversed antinociception, while gabapentin induced short-lasting antinociception. The levels of IL-1β, TNF-α, and IL-6 were reduced, while IL-10 was enhanced on sciatic nerve and spinal cord by treatment with CM and MSCs. Preliminary analysis of the CM secretome revealed the presence of growth factors and cytokines likely involved in the antinociception. In conclusion, the CM, similar to injection of live cells, produces a powerful and long-lasting antinociceptive effect on neuropathic pain, which is related with modulatory properties on peripheral and central levels of cytokines involved with the maintenance of this syndrome.

Quality control and immunomodulatory potential for clinical-grade equine bone marrow-derived mesenchymal stromal cells and conditioned medium

2020 ◽  
Vol 132 ◽  
pp. 407-415
Author(s):  
Fernanda Zettel Bastos ◽  
Fernanda Cristina Mendes Barussi ◽  
Lidiane Maria Boldrini Leite ◽  
Valderez Ravaglio Jamur ◽  
Amanda de Araújo Soares ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Quality Control ◽  
Conditioned Medium ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Clinical Grade ◽  
Immunomodulatory Potential ◽  
Equine Bone

Clinical-Scale Expansion of Human Bone Marrow-Derived Mesenchymal Stromal Cells to Treat Patients After Ischemic Stroke.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3021-3021
Author(s):  
Patrick J Hanley ◽  
Zhuyong Mei ◽  
Bing Yang ◽  
Osman Mir ◽  
Kaushik Parsha ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Ischemic Stroke ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Placebo Control ◽  
Human Mscs ◽  
Average Cell ◽  
Minimum Criteria

Abstract Abstract 3021 Ischemic stroke (IS) is the second leading cause of death worldwide and the leading cause of adult disability. IS patients have few options to limit neurological damage or augment the rehabilitation process. Tissue plasminogen activator, a fibrinolytic agent, is the only FDA approved therapy after IS but it must be administered within 3 hours of onset and is of limited benefit. Based on promising animal studies, another therapeutic option may be the application of mesenchymal stromal cells (MSCs). In one study, autologous MSCs were given to a subset of IS patients. This group showed better survival and neurological improvement, as judged by modified Rankin score and the Barthel index. A significant limitation to the use of autologous MSCs for acute stroke is that cells cannnot be transfused until at least 5 weeks after IS due to the time required for expansion in vitro. We hypothesize that treating patients with MSCs within 48 hours of a stroke may improve outcomes. We plan to expedite the time-to-infusion in two ways. First, banked allogeneic MSCs will be used instead of autologous MSCs to eliminate the production time and convert this to an off-the-shelf therapy. Second, we have compared the use of an automated cell culture device (the Quantum by Terumo BCT), which uses 2.1 m2 of hollow fibers in a bioreactor (equivalent to ∼120 T-175 cm2 flasks), to our current flask-based expansion method. In flasks, human bone marrow (BM) mononuclear cells (BMMC) were separated using the SEPAX device and were seeded at 5,000 BMMC/cm2 in T-175 cm2 flasks and split 1:4 when 70% confluent. After ∼1 month and 3–5 passages, ∼130 T-175 cm2 flasks were harvested and cryopreserved. In the Quantum, ∼25 mL of whole unprocessed BM was added to the bioreactor through a 200 μm filter. After 10 days, the cells were harvested and 2.0–3.5×107 cells were re-seeded in a new bioreactor at ∼1000 MSC/cm2 for a total culture time of ∼17 days. After 3–4 passages in flasks, an average of 2.69×108 MSCs were expanded from three independent BM donors. In two BM donors, MSCs harvested after 2 passages in the Quantum yielded an average of 8.75×108; these cells were frozen and can be used for subsequent expansions. MSCs expanded in both flasks and the Quantum were analyzed by flow cytometry and met the International Society of Cell Therapy (ISCT) minimum criteria for MSC (expression of CD73, CD105, CD90 etc). Expanded MSCs were sterile, were free from chromosomal abnormalities, and differentiated into adipocytes, chondrocytes, and osteoblasts. The production of 5×108 MSCs in flasks required 101 hours of labor compared to 21 hours with the Quantum. We estimated that during the manufacture of MSCs in flasks, there were 600 open (defined as exposing the system to the environment) events compared to 9 in the Quantum. To test the in vivo effects of manufactured MSCs, 24 aged male Long-Evans rats were randomized to receive flask-based human MSCs (P4) or saline vehicle at 7 days after stroke. At 28 days after stroke, animals treated with MSCs showed a significant reduction in neurological deficits compared with saline treated controls. In conclusion, in addition to the advantage of manufacture in a functionally- closed system, large numbers of MSCs expanded in the Quantum were available at a lower passage number with a higher average-cell yield at a slightly higher cost per 5×108 cells. When administered to rats with ischemic stroke, flask-based MSCs improved outcomes compared to placebo control treated animals. Whether MSCs expanded in the Quantum will function with equivalent efficacy is currently being tested and these data will be available for presentation in December. This project is supported by NHLBI-PACT, contract # HHSN268201000007C. Disclosures: Rice: Terumo BCT: Employment.

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