Cell therapies in the United States are regulated by the FDA’s Office of Cellular, Tissue, and Gene Therapies (OCTGT), part of the FDA Center for Biologics Evaluation and Research (CBER). Understanding these regulations is crucial for companies involved in the development and distribution of cellular products.

Overview of FDA Regulation

The FDA’s Center for Biologics Evaluation and Research (CBER) oversees:

• Cellular therapy products
• Human gene therapy products
• Certain devices related to cell and gene therapy

CBER operates under the authority of the Public Health Service Act and the Federal Food Drug and Cosmetic Act, which provide the legal framework for regulatory oversight.

Regulation Pathways: 351 vs. 361 Products

361 Products

Products that meet all criteria outlined in 21 CFR 1271.10(a) are classified as Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) under Section 361 of the Public Health Service (PHS) Act. These products, known as “361 products,” do not require FDA licensure or approval.

351 Products

Products that do not meet all criteria outlined in 21 CFR 1271.10(a) are regulated under Section 351 of the PHS Act and the Federal Food, Drug, and Cosmetic Act. These products are treated as drugs, devices, or biological products and require FDA approval through clinical trials to demonstrate safety and efficacy.

Regulatory Framework

The distinction between 361 and 351 products reflects the FDA’s assessment of relative risk associated with each type of cell therapy. 361 products are considered lower risk and are subject to less stringent regulatory requirements compared to 351 products, which undergo a rigorous approval process akin to pharmaceuticals.

Conclusion

Navigating FDA regulations for cell therapies involves understanding whether a product falls under the 361 or 51 pathway. Compliance with these regulations is essential for ensuring safety, efficacy, and legal market entry for cell therapy products in the United States.

Regenerative medicine is the cutting-edge “medicine of the future,” offering the promise of efficacy by enabling human tissue to be repaired, replaced, and healed (regenerated) once it is damaged or diseased. These therapies supplement the body’s natural healing mechanisms, often employing stem cells to stimulate the renewal of tissue damaged by injury, disease, or age. The rapid expansion of scientific knowledge offers great promise for advances in this field, holding vast potential to improve the quality of human life.

What are Stem Cells?

Stem cells are the basic building blocks of life. They are unspecialized cells capable of producing more stem cells through mitosis or differentiating into specialized cells that perform specific functions in the body. Stem cells are found throughout the body’s tissues, organs, and systems, although usually in small quantities in adults.

What are Hematopoietic Stem Cells?

Hematopoietic stem cells (HSCs) can give rise to all types of blood cells, including red blood cells, white blood cells, and platelets. They are particularly useful in treating blood-related diseases and conditions.

What are Mesenchymal Stem Cells?

Mesenchymal Stem Cells (MSCs) are multipotent stromal cells that are non-blood forming stem cells capable of differentiating into a variety of cell types, including muscle, bone, cartilage, and fat cells. When introduced into a patient’s body, MSCs can repair or replace damaged or degenerating tissue by communicating with surrounding cells, triggering a cellular cascade of healing (paracrine signaling).

The term MSC was coined in the late 1980s by Dr. Arnold Caplan of Case Western Reserve. Recently, Caplan redefined the acronym to “Medicinal Signaling Cell” to emphasize these cells’ role in secreting powerful bioactive molecules involved in cellular signaling and regeneration. Caplan now describes MSCs as a “multisite-regulatory dispensary” (Natural Drug Store).

The production of MSCs in the human body can be precipitated by bioactive placental tissues containing Growth Factors, Cytokines, and other powerful bioactive agents that trigger cell signaling. The remarkable ability of MSCs makes them irreplaceable in medical treatments.

What are Accessible Sources of Stem Cells?

Stem cells can be extracted from various parts of the body, such as bone marrow and adipose tissue. More recently, birth tissues from live births, including umbilical cord blood, cord tissue with Wharton’s Jelly, and amniotic membrane tissue, have been found to be rich sources of both HSCs and MSCs. These tissues also precipitate the production of MSCs through paracrine signaling. Growth Factors, Cytokines, Exosomes, and micro-RNA from birth tissues give rise to stem cells in this way. These cells, as well as MSCs contained in Wharton’s Jelly, tend to be more fit than those obtained from adult stem cells.

Wharton’s Jelly

Wharton’s Jelly is a gelatinous substance found in the umbilical cord that is rich in stem cells. Studies have shown that mesenchymal stem cells (MSCs) derived from Wharton’s Jelly have low immunogenicity. Human umbilical cord Wharton’s Jelly provides a new source for MSCs that are highly proliferative and have multi-differentiation potential. Wharton’s Jelly Cells (WJCs) express MSC markers but have low levels of human leukocyte antigen (HLA)-ABC and no HLA-DR. WJCs have low functional immunogenicity, and recipient rejection has not been documented.

Advanced Regenerative Medicine

Advanced Regenerative Medicine involves the use of regenerative biomolecules, tissue engineering, and stem cells to treat diseased or injured tissues. This field leverages cutting-edge techniques to promote healing and regeneration, offering new hope for patients with previously untreatable conditions.

Stem cells have captured the imagination of both scientists and the public alike with their potential to revolutionize medical treatments and therapies. The ability of these microscopic entities to differentiate into various cell types holds promise for curing diseases and repairing damaged tissues.

Understanding Stem Cell Differentiation

Researchers are actively exploring methods to manipulate stem cell development, particularly pluripotent cells capable of becoming any cell type. By culturing these cells in specific environments, scientists have observed activation of genes that dictate tissue specialization. This insight is crucial for developing targeted therapies and treatments.

Innovations in Stem Cell Research

Recent breakthroughs include the generation of dopamine-producing neurons from pluripotent cells and the creation of sugar-based scaffolds for blood vessels. These advancements highlight the potential of stem cells to address complex medical challenges.

Clinical Applications of Adult Stem Cells

Physicians have increasingly utilized adult stem cells sourced from fat or bone marrow to treat degenerative conditions such as knee osteoarthritis, sports injuries, and frozen shoulder. Unlike pluripotent cells, adult stem cells primarily function by releasing growth factors, proteins, and anti-inflammatory substances that promote tissue regeneration and healing.

Natural Healing Through Cellular Environment

In clinical settings, adult stem cells influence their environment by enhancing local cell growth and differentiation. This natural process mimics laboratory findings, demonstrating the body’s innate ability to harness its own healing potential.

Conclusion

The field of stem cell research continues to evolve, promising new avenues for medical intervention and patient care. By understanding how stem cells interact with their environment, researchers and healthcare providers can optimize therapies and explore novel treatments for a range of conditions

Introduction to PRP in Regenerative Medicine

In the regenerative medicine specialty, we have been active for about 8 years. Like many others, we started by using Platelet-Rich Plasma (PRP). We learned about it, were fascinated by it, and treated our patients with it. Patients loved it, and so did we.

PRP, if obtained and used correctly, is a powerful tool to implement in any medical practice, especially when dealing with the elderly, osteoarthritis, wear and tear of tendons and ligaments, and loss of vitality. PRP is also frequently used in plastic and reconstructive surgery for wound care, scar improvement, and overall skin rejuvenation.

How PRP Works

But why does PRP work, and how?

We are all familiar with platelets. They have significant power and influence over tissue regeneration, and by concentrating them in a blood sample, we can obtain signaling proteins, cytokines, and growth factors. If we add white blood cells to the mix, we get what is called L-PRP (leukocyte-rich PRP), making that “soup” even more interesting.

What is Photobiomodulation?

To harness the power of these bioactive substances, we need to coax the cells into releasing them. Normally, platelets are activated by the addition of calcium or by contact with collagen. However, several studies have demonstrated the influence of low-intensity laser on the activity of some cells. This effect is called “photobiomodulation.” This modality uses non-ionizing light sources, like LEDs or Helium-Neon lasers, to produce photochemical events at various biological scales. It has been demonstrated that this light reacts with the enzyme cytochrome c oxidase, which is paramount in mitochondrial processes.

Effects of Photobiomodulation on Cellular Cultures

Several scientists studied this light and its effects on cellular cultures. They found that cells proliferate more when exposed to low-level laser and showed increased viability.

We compared the levels of cytokines and growth factors in an irradiated sample and a non-irradiated one. Some growth factors even tripled in concentration after laser exposure. The famous interleukin-10, an anti-inflammatory protein, doubled in levels, and endorphins were released in high levels.

Benefits of Photobiomodulation

The photobiomodulation process has been established to provide extraordinary benefits in pain management, inflammation reduction, immunomodulation, and promotion of wound healing and tissue regeneration. It plays a fundamental part in our protocols.

Isn’t it all sort of amazing?

We’ll see you in the next blog. Keep your cells healthy!