Immunomodulatory oligonucleotide IMT504: Effects on mesenchymal stem cells as a first-in-class immunoprotective/immunoregenerative therapy

Abstract

The immune responses of humans and animals to insults (i.e., infections, traumas, tumoral transformation and radiation) are based on an intricate network of cells and chemical messengers. Abnormally high inflammation immediately after insult or abnormally prolonged pro-inflammatory stimuli bringing about chronic inflammation can lead to life-threatening or severely debilitating diseases. Mesenchymal stem cell (MSC) transplant has proved to be an effective therapy in preclinical studies which evaluated a vast diversity of inflammatory conditions. MSCs lead to resolution of inflammation, preparation for regeneration and actual regeneration, and then ultimate return to normal baseline or homeostasis. However, in clinical trials of transplanted MSCs, the expectations of great medical benefit have not yet been fulfilled. As a practical alternative to MSC transplant, a synthetic drug with the capacity to boost endogenous MSC expansion and/or activation may also be effective. Regarding this, IMT504, the prototype of a major class of immunomodulatory oligonucleotides, induces in vivo expansion of MSCs, resulting in a marked improvement in preclinical models of neuropathic pain, osteoporosis, diabetes and sepsis. IMT504 is easily manufactured and has an excellent preclinical safety record. In the small number of patients studied thus far, IMT504 has been well-tolerated, even at very high dosage. Further clinical investigation is necessary to demonstrate the utility of IMT504 for resolution of inflammation and regeneration in a broad array of human diseases that would likely benefit from an immunoprotective/immunoregenerative therapy.

Exosomes May Be the Potential New Direction of Research in Osteoarthritis Management

“…Therapeutic purposes are achieved by the local transplantation of autologous or allogeneic stem cells in vivo. MSCs have great anti-inflammatory and tissue repair effects [53]. In preceding studies, MSC has an excellent effect on heart disease, kidney disease, lung disease, nervous system disease, bone injury, and OA [54–59].…”

“…There are still serious problems in immune rejection and ethics when MSCs are transplanted into damaged organisms [62]. In addition, economic, regenerative, and security issues remain issues of concern [53]. Of note, it is generally believed that the paracrine function of mesenchymal stem cells plays a major role, and its secretions have strong immunoregulatory effects, such as extracellular vesicles, exosomes, and cytokines, of which exosomes is an important substance [63].…”

DNA‐Based Biomaterials for Immunoengineering

“…Transplantation of mesenchymal stem cells presents a promising therapeutic strategy to regenerate the immune system. Immunoregenerative ODN can induce the proliferation of mesenchymal stem cells and therefore it is a promising therapy for degenerative immune diseases …”

The potential ameliorative effect of Bone marrow Derived Mesenchymal Stem Cells on Cyclophosphamide Injured Lung in Adult Female Albino Rats

“…Mesenchymal stem cells (MSCs) have the characteristics of self-renewal and have the ability to differentiate into different lineage mesoderm, ectoderm and endoderm [6] , MSCs can be derived from adipose tissue, bone marrow, umbilical cord, and others [7] . MSCs have the ability to treat a variety of diseases such as inflammatory, myocardial ischemia, systemic lupus erythematosus, end-stage liver disease, and ischemic stroke in addition to its periodontal regeneration effect [8,9,10,11] . Moreover, several previous studies discussed the regulatory effects of stem cell factors on different immune cells including dendritic cells DCs, macrophages, natural killer cells NK neutrophils, B cells, and T cells [12,13] .…”