Current State and Issues of Regenerative Medicine for Rheumatic Diseases

Abstract

The prognosis of rheumatic diseases is generally better than that of malignant diseases. However, some cases with poor prognoses resist conventional therapies and cause irreversible functional and organ damage. In recent years, there has been much research on regenerative medicine, which uses stem cells to restore the function of missing or dysfunctional tissues and organs. The development of regenerative medicine is also being attempted in rheumatic diseases. In diseases such as systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and rheumatoid arthritis, hematopoietic stem cell transplantation has been attempted to correct and reconstruct abnormalities in the immune system. Mesenchymal stem cells (MSCs) have also been tried for the treatment of refractory skin ulcers in SSc using the ability of MSCs to differentiate into vascular endothelial cells and for the treatment of systemic lupus erythematosus SLE using the immunosuppressive effect of MSCs. CD34-positive endothelial progenitor cells (EPCs), which are found in the mononuclear cell fraction of bone marrow and peripheral blood, can differentiate into vascular endothelial cells at the site of ischemia. Therefore, EPCs have been used in research on vascular regeneration therapy for patients with severe lower limb ischemia caused by rheumatic diseases such as SSc. Since the first report of induced pluripotent stem cells (iPSCs) in 2007, research on regenerative medicine using iPSCs has been actively conducted, and their application to rheumatic diseases is expected. However, there are many safety issues and bioethical issues involved in regenerative medicine research, and it is essential to resolve these issues for practical application and spread of regenerative medicine in the future. The environment surrounding regenerative medicine research is changing drastically, and the required expertise is becoming higher. This paper outlines the current status and challenges of regenerative medicine in rheumatic diseases.

Serum-free Quality and Quantity Control Culture Improves the Angiogenic Potential of Peripheral Blood Mononuclear Cells Harvested from Patients with Connective Tissue Diseases

“…In mice with SLE, the number and angiogenic function of EPCs in PB were decreased, in agreement with a previous report 11) . However, there was no significant difference in the number of EPCs in human healthy controls and patients with CTD, although many studies have reported a decrease in the number of EPCs in patients with CTD 6,11,12) . One reason for this inconsistency would be that we included patients with CTD with a variety of disease levels and medications in this study.…”

Novel cell therapy with ex vivo cultured peripheral blood mononuclear cells significantly impacts angiogenesis in the murine ischemic limb model

“…Since the identification of endothelial progenitor cells (EPCs), autologous mononuclear cells (MNCs) have been used in clinical vascular regenerative therapy [ 1 , 2 ]. Despite confirming its safety in clinical trials, autologous EPC therapy shows limited effectiveness in treating certain diseases including diabetes and connective tissue disorders, primarily due to insufficient numbers and impaired function of EPCs [ [3] , [4] , [5] ]. To overcome these problems, various methods have been developed for the ex vivo expansion of EPCs.…”

Fabrication of a Tailored, Hybrid Extracellular Matrix Composite

“…[ 15 ] Allografts and xenografts, on the other hand, have potential ethical and immunological issues that limit transplant therapy as a medical treatment option. [ 16,17 ] Due to the composition and the architectural complexity of native ECM, the use of a single or a few components in the fabrication of tissue scaffolds cannot fully recapitulate its properties, restricting the production of a standardized structure composed of identical components or a universally applicable scaffold. Our study developed a new method for transforming the architecture of native tissue obtained from living tissue into an implantable scaffold engineered from a single cell type (i.e., fibroblast) to be transferable to various scaffolds, which can be applicable to multiple tissues and organs.…”