A number of different stem cell types have been shown to exert significant therapeutic effects when transplanted into the central nervous system. These cells include non-hematopoietic stem cells such as mesenchymal stem cells and neural/progenitor stem cells and carry out their effects by secreting what are known as neurotrophic paracrine factors, whichhelp to control the immune system.
In recent years, it has been suggested that rather than requiring the injection of stem cells, brain injury repair may be achieved by injecting the molecules that stem cells tend to secrete – known as secretome. The stem cell secretome includes growth factors as well as cytokines and chemokines. Investigators have begun to explore whether delivering these substances, rather than stem cells, could offer a more efficient means to therapy.
The rationale is that by delivering these substances directly, it should be possible to stimulate the proliferation of progenitor cells in the central nervous system and therefore instigate repair. However, initial studies have shown that the infusion of individual cytokines does not have the expected effect. According to the authors of a review published in Biochimie, it may be that multiple substances will need to be simultaneously infused in pre-tested concentrations so that they can act synergistically to optimize therapeutic effects.
Clinical trials are underway to determine the safety to patients of the secretome approach and to identify any relevant risks so that potential risks can be weighed against potential benefits of this type of therapeutic approach. There is also research on a wide variety of topics that will need clarification if effective stem cell secretome therapies are to be developed for brain repair. These topics include clarifying aspects of tissue transport and determining the mechanisms by which secretomes confer their benefits.
Reference: Drago, D. (2014). The stem cell secretome and its
role in brain repair. Biochimie, 95(12),
2271-2285.
Stem cell therapy is used for a broad range of applications, including the treatment of injuries and chronic conditions. Before undergoing this form of therapy, many patients are naturally inclined to explore any possibilities which could enhance the effectiveness of treatment. One option which is sometimes posed to patients is voluntary fasting – but is there really any benefit to fasting prior to stem cell treatment?
What the Research Says
In May of 2018, MIT biologists announced that they’d made a groundbreaking discovery: according to their research, it appeared that fasting could boost stem cells’ regenerative capacity. In an animal study, fasting spurred cells to break down fatty acids instead of glucose, which stimulates stem cells to become more regenerative.
Yet, the evidence only showed the metabolic switch taking place in the intestinal stem cells. After mice fasted for 24 hours, the researchers removed intestinal stem cells and grew them, finding that the fasting doubled the cells’ regenerative capacity.
Unfortunately, while this finding could hold value for patients recovering from gastrointestinal infections or other conditions affecting the intestine, as of yet, there is no concrete evidence which suggests it could benefit patients receiving stem cell therapy for other conditions. For instance, someone who is undergoing stem cell therapy to treat a musculoskeletal injury may likely yield no benefit from fasting, as the enhanced regenerative effects have only been observed in intestinal cells.
Further Studies Are Needed
Aside from the study’s limited scope, the research leader himself also indicated that the findings are still too narrow for drawing concrete conclusions. When interviewed for a publication in Medium, senior author of the study and assistant professor of biology, Omer Yilmaz, said that while stem cells do indeed use fat for energy to improve function, “the next step is to work to understand why that is.” He also added that “with these types of interventions, there’s never one simple answer.”
For now, there appears to be too much uncertainty to recommend fasting prior to stem cell therapy. Because these findings have not been observed in any humans, and those that have been observed were concentrated to intestinal cells, anyone who is receiving stem cell therapy can consider that eating beforehand is possibly unlikely to play any role in altering the results of their treatment.
The human skeleton is made up of bone, cartilage, fat, nerves, blood vessels, and bone marrow. While the skeleton is usually strong and vibrant in youth, it changes considerably with age. Many people, especially women, experience demineralization of bone called osteoporosis. Most of us will suffer from painful, stiff, arthritic joints either from osteoarthritis or rheumatoid arthritis or both. While some of the diseases of bone and joints have specific treatments, none of them helps to restore bone and joints to their younger state. If one could reintroduce skeletal stem cells into the body, that could all change. Excitingly, researchers have recently isolated human skeletal stem cells from bone and other tissues.
At first glance, this breakthrough may not seem so surprising. One might wonder: didn’t we already have stem cells that form bone and cartilage? The answer is yes, but with an important caveat. Before researchers recently isolated human skeletal stem cells, the only stem cells that could be used to produce bone and cartilage were rather unpredictable. In addition to bone and cartilage, the mesenchymal stem cells that have been long used to form these tissues could also produce fat, muscle, fiberglass, blood vessel cells, and other tissues. In other words, the stem cells were broadly multipotent and, by extension, could not easily be used for a specific purpose, like mending bone or repairing an arthritic joint. That is why the recent discovery of these particular skeletal stem cells is so important.
The researchers isolated skeletal stem cells from various human tissues, mainly bone. They then used the skeletal stem cells to regrow bone and/or cartilage. Not only did the stem cells produce bone and cartilage in the first animal they tested, but they could retrieve stem cells from that animal and then cause bone to regrow in a second animal. This means that the skeletal stem cells have the capability of reproducing themselves.
The same researchers also discovered that when a skeleton is injured, such as in a bone fracture, the number of skeletal stem cells in that area increases dramatically. This makes sense since these cells are used to repair and regrow bone. It is also a promising result because it suggests that stem cells could be used to accelerate bone and joint healing in humans.
Scientists not directly involved in this research heralded this finding as “an extremely important advance.” However, they also acknowledge that more work needs to be done before skeletal stem cells can be routinely used in patients with orthopedic conditions. Nevertheless, these results are an exciting development in the field of stem cell research and orthopedics.
Perinatal stem cells have been attracting attention globally in recent years due to their potential in regenerative medicine. These stem cells come in many forms, due to the wide variety of potential sources for these cells. Perinatal stem cells, for instance, may be umbilical cord-derived hematopoietic stem cells, amniotic epithelial cells, amniotic fluid stem cells, or chorionic mesenchymal stem cells. All sources, nonetheless are considered biological waste and are therefore usually discarded after delivery of babies.
Importantly, perinatal stem cells, despite their origin, tend to share a number of characteristics that make them beneficial in treating conditions. Additionally, unlike other sources of stem cells, retrieval of perinatal stem cells is noninvasive and does not require the ethical considerations that retrieval from other sources may involve. A recent review in Regenerative Medicine has highlighted the potential benefits of perinatal stem cells in therapeutic interventions.
In addition to the relatively easy collection and preparation of perinatal stem cells, these cells tend to be easily harvested and manipulated without harming either the mother or the baby. Upon collection, these stem cells exist in high volume and have greater ability to proliferate than other stem cell types such as bone marrow stem cells. Research has also shown that these cells tend not to lead to adverse immune reactions, though the mechanisms involved in their relationship to the immune system are not well understood.
Given their relative advantages over other stem cell types, perinatal stem cells are well poised to be used in cell-based therapies targeting a wide variety of conditions. Future research will help to define the precise role these cells can play in regenerative medicine and which conditions they may be most useful for.
Bone generally develops via one of two distinct mechanisms: intramembranous ossification and endochondral ossification. In the former case, mesenchymal progenitor cells directly differentiate into osteoblasts that form bone. In the latter case, the mesenchymal progenitor cells first create a matrix of cartilage that then acts as a template to enable the remodeling or development of bone tissue. This process of endochondral ossification is the predominant way that bone is generating during the healing process after bones are broken and fractures are endured. Using stem cells to facilitate this process can, therefore, be beneficial in non-healing bone fractures.
A new study published in Acta Biomaterialia has proposed that adipose tissue can be used in bone generation as a scaffold on which adipose mesenchymal stem cells can expand and allow for endochondral ossification. The researchers showed how adipose tissue could be used in this way, through what they termed Adiscaf, to successfully generate cartilage tissue and eventually bone tissue formation. The bone tissue that formed through this process contained bone marrow elements, further demonstrating the bone’s integrity and the promise of this procedure.
Compared to other strategies for building scaffolding, this strategy appeared successful because by using adipose tissue, the adipose stem cells were exposed to their native environment and therefore likely maintained functions they otherwise may not have. Not only will these findings help to solidify our understanding of how to nurture stem cells and enable them to differentiate in ways that can be therapeutically applicable, but they also specifically show how adipose tissue may be able to be used to generate a bone organ through endochondral ossification. Future research will likely help to clarify how these findings can be applied to patients to improve bone healing.
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