Stem cell therapy in aging and degenerative diseases: A closer look at regenerative medicine

July 28, 2024

Healthcaretoday, AIMM, Regenerative medicine, stem cells, cell death, aging, degenerative diseases, apoptosis, mitochondrial depletion, oxidative stress, neurodegeneration, stroke recovery, spinal cord injury, stem cell therapy, tissue engineering, cancer therapy, medical ethics, chronic disease, healthspan, wellbeing, biomedical research, medical innovation,

Aging is an inevitable part of life, characterized by various biological changes, including genetic mutations, oxidative stress, mitochondrial depletion, and damage to cellular structures. These changes contribute to the gradual decline in bodily functions, leading to degenerative diseases. At the heart of these processes is cell death, a complex phenomenon that has intrigued scientists and medical professionals for decades.

Regenerative medicine has emerged as a promising field aiming to slow down or even reverse cell death, thereby promoting health and longevity. But is it truly beneficial to interfere with the natural process of cell death? Is it necessary to slow it down, or is this interference a dangerous game?

The necessity of cell death: A crucial biological process
"Cell death is an important process in the body because it strikes a balance," explains Professor Dr Ramamurthy Subramaniam (pix), Head of the Department at the International Institute of Wellness & Aesthetic Medicine. Speaking at the Association of Integrative Medicine Malaysia (AIMM)’s 5th International Integrative Medicine Conference 2024, themed "Healthspan - The Science and Art of Wellbeing," Dr Ramamurthy emphasized that without a balance between cell death and cell regeneration, the body could spiral into chaos.

There are several mechanisms of cell death, including apoptosis, necroptosis and pyroptosis. Each of these plays a critical role in maintaining the body's homeostasis. Apoptosis, for instance, is a linear, predictable process that, much like gravity, will occur inevitably. The real question is: How much control should we exert over apoptosis, and are we overstepping by trying to manipulate this process through regenerative medicine?

Degenerative diseases: The toll of aging
Degenerative diseases are characterized by the gradual deterioration of function and structure in affected body parts, often leading to disability, morbidity, and mortality. At the cellular level, aging and the accumulation of DNA damage are significant risk factors. These conditions are often chronic, age-related, and influenced by genetic and lifestyle factors. Unfortunately, some individuals experience premature degeneration, leading to early-onset diseases.

Stem cells: The foundation of life
Stem cells are the building blocks of all living organisms. These unspecialized cells have the unique ability to develop into any specialized cell type, and they can replicate numerous times to repair and replenish tissues. In humans, there are nearly 220 different cell types, all functioning symbiotically. The differentiation of stem cells into specialized cells is influenced by various factors, including the formulation or source of the stem cells, the route of administration, and the recipient's medical condition.

“When covering a degenerative condition using stem cells, understanding the source, route of administration, and the medical condition is crucial. Once stem cells are infused or injected into the body, they decide their next course of action,” explains Dr Ramamurthy.

Regenerative medicine: A new frontier in healing
Regenerative medicine is a broad field that not only encompasses cellular or tissue engineering but also incorporates self-healing. This approach involves stimulating the body’s own systems, sometimes with the help of foreign biological material, to insult, recreate, and restore cells, tissues, and organs. The field includes stem cell therapy, platelet-rich plasma (PRP), lipogems, and prolotherapy, with the overarching goal of finding cures rather than merely treating chronic diseases.

The mechanisms behind regenerative medicine
The mechanism of action of Adult Mesenchymal Stem Cells (MSCs) in regenerative medicine includes trans-differentiation, cell fusion, mitochondrial transfer, and extracellular vesicles and cellular communication. These processes are integral to combating degenerative diseases, such as neurodegenerative, vascular, osteodegenerative, and macular degenerative diseases, as well as cancers.

Stroke and spinal cord injuries: Stem cell therapy’s success stories
Stem cell therapy has shown promising results in treating stroke and spinal cord injuries. However, the process is not as simple as infusing stem cells and expecting miraculous results. "You have to rewire the lesion frame when inducing stem cells into an ischemic stroke or hemorrhagic stroke patient," says Dr Ramamurthy. This rewiring involves transcranial electrical stimulation, vagus nerve stimulation, and other methods to stimulate the brain to receive the cells and recover from the damage.

Methods of stem cell delivery in stroke patients
There are various methods for delivering stem cells to stroke patients, each with its own set of challenges. These methods include:

Intracerebral (IC) injection: This invasive technique offers precise cellular delivery but results in poor cell distribution in the target lesion. Adverse events such as seizures, syncope, and motor worsening have been reported.
Intracisternal/ Cerebroventricular (ICV) delivery: Less invasive than IC, this method also comes with risks, including fever and meningeal signs post-delivery.

Types of stem cells used in stroke therapy
Different types of stem cells are used in stroke therapy, each with distinct advantages and limitations:

Umbilical cord stem cells: These are readily available but require specialized labs for processing.
Embryonic stem cells: While they have the potential for neural replacement, ethical concerns and the risk of teratoma formation are significant drawbacks.
Induced pluripotent stem cells (iPSCs): These cells offer the advantage of reduced immune rejection but are not readily available in acute settings and also carry the risk of teratoma formation.

Timing and dosage: The critical factors in stem cell therapy
The timing of stem cell administration is crucial, with studies suggesting that the sooner, the better. However, there are no clearly defined therapeutic time windows. Dosage is another critical factor, with preclinical studies showing a dose-response relationship. The optimal dose for intravenous (IV) or intra-arterial (IA) therapy remains unclear, highlighting the need for further research.

Dr Ramamurthy recounts the case of a 45-year-old man who suffered a brain hemorrhage, leading to paralysis and loss of speech. Two and a half years later, after undergoing a series of stem cell treatments and brain rewiring, the patient regained some mobility and was able to cycle again. This case underscores the potential of stem cell therapy, even in severe conditions.

Beyond stroke: Stem cell therapy’s expanding horizons
Stem cell therapy is not limited to stroke and spinal cord injuries. It has also shown promise in treating acute renal failure, HIV, type 1 diabetes, Alzheimer’s disease, motor neuron diseases, chronic wounds, and ischemic vascular diseases. The therapeutic potential of MSC-derived exosomes in wound healing, particularly in chronic diabetic ulcers, is especially noteworthy.

Cancer therapy: A cautious approach
The application of stem cells in cancer therapy is both promising and controversial. While some studies suggest that stem cells can help treat cancer, others warn of potential dangers. "The truth is, we do not know whether stem cells help or harm in cancer therapy," admits Dr Ramamurthy. He advises caution, emphasizing the importance of involving a team of oncologists in any treatment plan for cancer patients.

The ethical and medical limitations of stem cell therapy
Stem cell therapy is not without its limitations. Ethically, the exploitation of stem cell treatments by unscrupulous clinics is a significant concern. Medically, there are risks of cancer induction, graft-versus-host disease, and immunosuppression. Despite these challenges, the potential of stem cell therapy cannot be denied, but it must be approached with caution and a deep understanding of its complexities.

Regenerative medicine holds immense promise, particularly in the field of stem cell therapy. However, it is not a panacea. The complexities of cell death, the challenges of degenerative diseases, and the ethical considerations of stem cell use require careful navigation. As we continue to explore this frontier, the balance between innovation and caution will be crucial in determining the future of regenerative medicine.