Cellular transplantation and platelet-rich plasma injections for discogenic pain: a contemporary review

Degenerative disc disease (DDD) is the leading cause of chronic back pain. It is a pathologic condition associated with aging and is believed to result from catabolic excess in the intervertebral discs’ (IVD) extracellular matrix. Two new treatment options are intradiscal cellular transplantation and growth factor therapy. Recent investigations on the use of these therapies are discussed and compared with emerging evidence supporting novel cellular injections. At present, human and animal studies provide a compelling rationale for the use of cellular injections in the treatment of discogenic pain. Since DDD results from the IVD extracellular matrix’s unmitigated catabolism, cellular injections are used to induce regeneration and homeostasis in the IVD. Here, we review intervertebral disc anatomy, DDD pathophysiology and clinical considerations, as well as the current and emerging literature investigating outcomes associated with cellular transplantation and platelet-rich plasma for discogenic pain. Further high-quality trials are certainly warranted.

Progress in Translational Regulatory T Cell Therapies for Type 1 Diabetes and Islet Transplantation

Regulatory T cells (Tregs) have become highly relevant in the pathophysiology and treatment of autoimmune diseases, such as type 1 diabetes (T1D). As these cells are known to be defective in T1D, recent efforts have explored ex vivo and in vivo Treg expansion and enhancement as a means for restoring self-tolerance in this disease. Given their capacity to also modulate alloimmune responses, studies using Treg-based therapies have recently been undertaken in transplantation. Islet transplantation provides a unique opportunity to study the critical immunological crossroads between auto- and alloimmunity. This procedure has advanced greatly in recent years, and reports of complete abrogation of severe hypoglycemia and long-term insulin independence have become increasingly reported. It is clear that cellular transplantation has the potential to be a true cure in T1D, provided the remaining barriers of cell supply and abrogated need for immune suppression can be overcome. However, the role that Tregs play in islet transplantation remains to be defined. Herein, we synthesize the progress and current state of Treg-based therapies in T1D and islet transplantation. We provide an extensive, but concise, background to understand the physiology and function of these cells and discuss the clinical evidence supporting potency and potential Treg-based therapies in the context of T1D and islet transplantation. Finally, we discuss some areas of opportunity and potential research avenues to guide effective future clinical application. This review provides a basic framework of knowledge for clinicians and researchers involved in the care of patients with T1D and islet transplantation.

Combinatorial Immunotherapies for Metastatic Colorectal Cancer

Colorectal cancer (CRC) is one of the most frequent and deadly forms of cancer. About half of patients are affected by metastasis, with the cancer spreading to e.g., liver, lungs or the peritoneum. The majority of these patients cannot be cured despite steady advances in treatment options. Immunotherapies are currently not widely applicable for this disease, yet show potential in preclinical models and clinical translation. The tumour microenvironment (TME) has emerged as a key factor in CRC metastasis, including by means of immune evasion—forming a major barrier to effective immuno-oncology. Several approaches are in development that aim to overcome the immunosuppressive environment and boost anti-tumour immunity. Among them are vaccination strategies, cellular transplantation therapies, and targeted treatments. Given the complexity of the system, we argue for rational design of combinatorial therapies and consider the implications of precision medicine in this context.

Stem cell therapies as a therapeutic option to counter chemo brain: a negative effect of cancer treatment

Chemo brain, a constellation of cognitive deficiencies followed by chemotherapy drugs, used to treat different types of cancers and adversely impacts the quality of life of a cancer survivor. The underlying mechanism of chemo brain remains vague, thus delaying the advancement of efficient treatments. Unfortunately, there is no US FDA approved medicine for chemo brain and often medicines considered for chemo brain are already the ones approved for other diseases. Nevertheless, researches exploring stem cell transplantation in different neurodegenerative diseases demonstrate that cellular transplantation could reverse chemotherapy-induced chemo brain. This review talks about the mechanism behind the cognitive impairments instigated by different chemotherapy drugs used in cancer treatment, and how stem cell therapy could be advantageous to overcome this disease.

Designer, injectable gels to prevent transplanted Schwann cell loss during spinal cord injury therapy

Transplantation of patient-derived Schwann cells is a promising regenerative medicine therapy for spinal cord injuries; however, therapeutic efficacy is compromised by inefficient cell delivery. We present a materials-based strategy that addresses three common causes of transplanted cell death: (i) membrane damage during injection, (ii) cell leakage from the injection site, and (iii) apoptosis due to loss of endogenous matrix. Using protein engineering and peptide-based assembly, we designed injectable hydrogels with modular cell-adhesive and mechanical properties. In a cervical contusion model, our hydrogel matrix resulted in a greater than 700% improvement in successful Schwann cell transplantation. The combination therapy of cells and gel significantly improved the spatial distribution of transplanted cells within the endogenous tissue. A reduction in cystic cavitation and neuronal loss were also observed with substantial increases in forelimb strength and coordination. Using an injectable hydrogel matrix, therefore, can markedly improve the outcomes of cellular transplantation therapies.

Stem cell activity in the repair of cardiovascular tissues

Stem cells can become different types of cells and have the potential to divide and self-renew. There are two types of stem cells, first the embryonic stem cells and second the adult stem cells, both help in regeneration or repair tissues of an organism, for this reason, the stem cells are being used to renew the world of medicine. Stem cells are obtained from three sources: the first can be our own body that where certain organs still have some cells still not completely differentiated. The second source is the embryos when they are in the blastocyst phase (between five to fourteen days from conception), and the third source can be in the cells of the skin, liver or another cell type that have been modified to behave like embryonic stem cells. With this therapy, we would find ourselves before an inexhaustible source to repair the tissues and organs that were damaged in our bodies. One of the main causes of mortality in heart failure, but with the help of cell therapy has been studied the repair of cardiac tissue with the stem cell transplant. The objective of the cellular transplantation is that the transplanted cells in the heart tissue manage to regenerate, renewed, and repair any part of the heart tissue damaged.

Subcutaneous DL Technique Has Proven To Be an Adequate Host for Human Embryonic Stem Cells

Islet transplantation has become an important treatment modality for Type 1 Diabetes Mellitus (T1DM); nonetheless, the procedure may be limited by donor availability. An alternative has been the increasing use of cellular therapies derived from human Embryonic Stem Cells (hESC), showing very promising results in maturation, yield and ultimately, in insulin secretion in response to adequate stimuli. We recently developed a new technique for cellular transplantation under the skin. This manuscript evaluates the capabilities of the pre-vascularized Device-Less (DL) site to allow transplantation of Pancreatic Endoderm (PE) cells differentiated from hESC to treat diabetes mellitus. Fifty immunodeficient mice, n = 25 diabetic and n = 25 non-diabetic, were transplanted with PE cells. Animals were followed for 22 weeks and grafts were retrieved to evaluate engraftment and subsequent maturation. Diabetic mice showed slightly better engraftment (48% vs. 36%, p = 0.19) and secreted higher concentration of human C-peptide upon glucose stimulation (0.32 ± 0.15 ng/mL vs. 0.13 ± 0.09 ng/mL, p = 0.30), although differences were not significant. This maturation was not sufficient to successfully reverse diabetes. Monomorphic cystic changes were detected in 12% and 8%, respectively (diabetics vs. non-diabetics, p = 0.32) and all grafts seemed to be adequately contained by the surrounding collagen wall within the DL space. Our findings support the capabilities of the DL site to host PE cells and allow safe maturation as a new strategy to treat diabetes.

Transplanting Cells for Spinal Cord Repair: Who, What, When, Where and Why?

Cellular transplantation for repair of the injured spinal cord has a rich history with strategies focused on neuroprotection, immunomodulation, and neural reconstruction. The goal of the present review is to provide a concise overview and discussion of five key themes that have become important considerations for rebuilding functional neural networks. The questions raised include: (i) who are the donor cells selected for transplantation, (ii) what is the intended target for repair, (iii) when is the optimal time for transplantation, (iv) where should the cells be delivered, and lastly (v) why does cell transplantation remain an attractive candidate for promoting neural repair after injury? Recent developments in neurobiology and engineering now enable us to start addressing these questions with multidisciplinary expertise and methods.