Adult Stem Cell (Somatic Stem Cell): Definition, Types, Established Uses and Evidence

An adult stem cell, also called a somatic or tissue-specific stem cell, is an undifferentiated cell found among the specialised cells of a mature tissue. It can renew itself and differentiate into the cell types of the tissue where it lives [1]. Adult stem cells are generally tissue-restricted and range from multipotent to unipotent. Embryonic stem cells, by contrast, are pluripotent [2]. Blood stem cell transplantation is the established therapeutic use. Skin and cornea applications are also recognised, and most other uses remain experimental [12].

Definition and core properties of adult stem cells

Adult stem cells are found in many organs, including bone marrow, brain, skeletal muscle and skin [1]. Two properties define them:

• Self-renewal: they divide to maintain their own population over long periods.
• Differentiation: they produce progenitor cells that mature into the specialised cells of their tissue [1].

Stem cells usually sit in a specific microenvironment called a niche. The niche controls when the cells become active, which balances keeping the stem cell pool against producing new progenitor cells [3]. The word "adult" means the cells come from tissue after embryonic development. It does not mean they only exist in adults. The synonyms "somatic" and "tissue-specific" stress that the cells belong to body tissues and are generally committed to their tissue of origin.

Main types of adult stem cells

Adult stem cells vs embryonic stem cells: potency

Potency describes how many cell types a stem cell can produce. Embryonic stem cells are pluripotent: they can give rise to nearly all cell types of the body. Adult stem cells are generally multipotent, producing several cell types of one tissue, or unipotent, producing only one [2]. A 2013 review in Stem Cells International describes one exception. Spermatogonial stem cells from the adult testis have been reported to be the only body cells that can be reprogrammed to a pluripotent state in vitro without added factors [2]. Because they are more limited, adult stem cells are used mainly to rebuild the tissue they came from. That is the case in blood stem cell, skin and cornea therapies.

Hematopoietic stem cell transplantation: the established clinical use

Hematopoietic stem cells are the most thoroughly characterised adult stem cells. Researchers identified them in the early 1960s as the cells responsible for successful bone marrow transplants [1]. They are rare: about one in every 10,000 bone marrow cells [1]. This makes them hard to purify. A transplant therefore also carries other cells, including donor immune T cells, which can cause graft-versus-host disease [1].

E. Donnall Thomas and colleagues reported the first intravenous bone marrow infusions in patients in 1957 [6]. Cumulative transplants worldwide passed 1 million in 2012 and were projected to reach about 1.5 million by 2019 [6]. For 2018, 1,768 transplant teams in 89 countries reported 93,105 hematopoietic cell transplants (HCT). Of these, 48,680 were autologous, using the patient's own cells, and 44,425 were allogeneic, using donor cells [5]. Allogeneic activity more than doubled between 2007 and 2018 [5].

• Autologous HCT: mainly for plasma cell disorders and lymphoma, and also some solid tumours [5].
• Allogeneic HCT: mainly for acute myeloid leukaemia, acute lymphoblastic leukaemia and myelodysplastic/myeloproliferative neoplasms [5].

The International Society for Stem Cell Research (ISSCR) states that blood stem cell transplantation has been used for more than 50 years. It can treat some blood and immune disorders and some cases of acquired bone marrow failure [12].

Mesenchymal stromal cells: widely studied, mostly investigational

Mesenchymal stromal cells (often called mesenchymal stem cells) can be isolated from many tissues [2]. In 2006, the International Society for Cellular Therapy proposed minimal criteria to make studies comparable [4]:

1. the cells stick to plastic in standard culture;
2. they carry the surface markers CD105, CD73 and CD90 and lack markers such as CD45, CD34, CD14 or CD11b, CD79α or CD19, and HLA-DR;
3. they can turn into osteoblasts, adipocytes and chondroblasts in vitro.

Many MSC trials have shown only marginal benefits. Some researchers think any effects come mainly from signalling molecules the cells release (paracrine effects) rather than from rebuilding tissue. MSCs have also been shown to support tumour growth in some settings, which is a safety concern [2].

On 18 December 2024, the US Food and Drug Administration (FDA) approved remestemcel-L-rknd (Ryoncil). It is an allogeneic MSC product made from bone marrow. It is approved only for steroid-refractory acute graft-versus-host disease in patients aged 2 months and older. FDA described it as the first FDA-approved MSC therapy [7]. The approval rested on a single-arm study of 54 children. It found a 70% overall response rate at day 28, and the median duration of response was 54 days [7]. Separate worldwiki.io pages cover adipose-derived stem cells and the stromal vascular fraction.

Skin and cornea: tissue-specific regeneration

The ISSCR notes that skin and cornea transplants depend on stem cells naturally present in those tissues for long-term healing [12]. Holoclar is made from the patient's own corneal epithelial cells, including limbal stem cells. A small biopsy is taken from an undamaged part of the eye, the cells are expanded in the laboratory, and then they are grafted onto the damaged cornea [10]. The European Medicines Agency (EMA) described it as the first stem-cell therapy recommended for approval in the EU [10]. It received conditional marketing authorisation on 17 February 2015 for adults with moderate to severe limbal stem cell deficiency caused by physical or chemical eye burns. The authorisation became a standard one on 22 February 2024 [11].

The plasticity debate

Around 2000, several reports suggested that bone marrow cells could turn into liver, heart, nerve and blood vessel cells. This idea is called trans-differentiation or plasticity. Most of those reports could not be confirmed in later studies [3]. Other explanations include donor cells fusing with host cells [3], and cell preparations containing more than one type of stem cell rather than a single cell with broad potency [1]. The debate is one reason claims that an adult stem cell injection can repair unrelated organs need careful scrutiny.

Risks, regulation and unproven stem cell clinics

The FDA warns patients not to use unapproved products made from human cells or tissues that are sold for a wide range of diseases. Such products are generally regulated as drugs and biological products, and the FDA has not reviewed their quality, safety, purity or potency. The agency has received reports of adverse events, including patient deaths [9]. In its consumer alert, the FDA says blood-forming stem cell products from umbilical cord blood are approved for disorders of blood production. It lists many conditions for which no stem cell or exosome product is approved, including:

• orthopaedic conditions such as arthritis and back or knee pain;
• neurological diseases such as multiple sclerosis, ALS, Parkinson's disease and Alzheimer's disease;
• heart and lung disease, autism, vision loss and chronic pain [8].

The alert was last updated in April 2024 [8], so it does not mention the MSC approval of December 2024 [7].

How to evaluate an adult stem cell treatment offer

The ISSCR lists warning signs and questions for patients [12]:

1. Be cautious if the main evidence is patient testimonials rather than published clinical research.
2. Be sceptical if one treatment is offered for many unrelated diseases.
3. Ask where the cells come from and how they are processed. This should be explained in the consent form.
4. Treat "no risk" claims as a red flag. All treatments carry risks.
5. Be wary of high fees. Legitimate clinical trials usually do not charge participants.
6. Ask whether an independent ethics board approved the treatment, and whether a regulator such as the FDA or EMA has authorised it.

Limits of current knowledge

Adult stem cell biology is still an active research area. The role of the niche, the true potency of individual cells, and how MSCs work are all still being studied [2][3]. Outside hematopoietic transplantation and a small number of authorised tissue-specific products, the evidence comes mostly from early-phase or small trials. Anyone considering treatment should discuss it with a specialist in the relevant disease.