The Need for Standardization in a Medical Tourism Context
Abstract
Medicinal signaling cells (MSCs) secrete bioactive molecules with paracrine effects. These cells are widely used in basic and clinical research to treat several human diseases and medically relevant conditions. Although there are promising results, only a few treatments are approved of its administration, and clinicians should not underestimate the potential risks of its application without proper authorization. However, some treatments advertised mainly through the internet are not supported by solid or rigorous scientific evidence, legal consent, or the assurance of safety and efficacy, especially in the cell therapy tourism space. This practice allows patients to travel from stringently regulated countries to less restricted ones and increase the flourishing of nonendorsed therapies in these regions. Clinical applications of MSC-based treatments are subject to health legislation, and regulatory agencies are responsible for supervising their manufacture, quality control, and marketing approval. Consensus is needed to homologize and strengthen health legislation regarding those therapies, particularly in regions where medical tourism is frequent. Latin America and the Caribbean, an overlooked region with very heterogeneous legislation regarding cell therapy, is a popular medical tourism destination. Brazil and Argentina created regulations to supervise cell-based treatment manufacture, quality, and marketing, while Mexico, considered the second-largest drug market in Latin America, does not recognize nor authorize any cell as therapy. Also, some regulatory bodies miss the importance of several critical good manufacture practice processes to ensure reproducible, reliable, safe, and potentially more favorable results and do not consider them in their legislation. These inconsistencies make the region vulnerable to unproven or unethical treatments, potentially becoming a public health problem involving people from countries worldwide. This review attempts to generate awareness for the legal status of cell therapies in Latin America and the need for standardization as this region is a significant medical tourism destination.
Introduction
Mesenchymal stem cells (MSC) are more recently and accurately called medicinal signaling cells (MSCs) due to their potential to secrete bioactive molecules [1,2]. Researchers study the paracrine effects of MSCs and the basis for their use to treat several human diseases and medical conditions [3]. MSCs have gained acceptance as allogeneic cells because of their immunomodulation properties [4,5]. In contrast to other cell therapies, MSCs can be obtained from different tissues in large quantities using relatively modest invasive methods and minor ethical considerations [6–8].
Also, MSCs could be available for a more significant number of patients for their capacity for ex vivo expansion to obtain an increased number of cells [9]. Manufacturers prefer allogeneic-based products due to the scale-up possibilities and the opportunity to introduce a large market through massive export [10]. However, this expansion is potentially dangerous for clinical application if it is not carefully controlled.
Despite the substantial amount of research for MSC treatments [11] and its promising results [12], regulatory agencies worldwide have approved less than 15 allogeneic MSC products for their clinical use [9,10,13]. Therefore, clinicians should not employ any treatment available underestimating the potential risks of its application [12]. Medical tourism is a practice that allows foreign patients to receive treatments that are unavailable or forbidden in their own country [13].
Through this practice, “stem cell-derived” treatments are extensively offered and commercialized without legal approval [14] or solid or rigorous scientific evidence [15,16]. Most of these therapies are not extensively evaluated, as they should be. Globalization and expensive health care of industrialized countries have contributed to medical tourism growth in developing countries [17,18]. For this, the current review discusses the development and importance of cell treatment tourism in these countries.
Explicit strategies for deploying medical tourism are absent in most destinations [17]. Moreover, the regulatory requirements for cellular therapy differ among countries, and this disparity is continuously growing because of the increasing number of cellular products available or in research [19]. To avoid harmful practices and offer better allogeneic MSC-derived treatments, it is necessary to improve standards and harmonize products and facilities’ specifications, evaluations, and regulations [20]. For this, it is crucial to understand the current regulatory landscape and what must be harmonized, especially in countries where medical tourism is popular such as Mexico, one of the world’s most important medical tourism destinations at present [17].
The definition and general legislation of cell products among Japan, the European Union (EU), and the United States have been outlined previously [20–22]. However, the international community had overlooked the regulation and legal status in Latin America, a region with a landscape of poor regulation [23] and a growing market for cell treatment tourism where researchers and practitioners have frequently neglected the day-to-day administration of cell therapy without legal approval.
In this study, we briefly analyze the rules and policies around cell treatment practice and enlist the laws, guidelines, decrees, or resolutions that regulate allogeneic MSC-based to compare them with the benchmark health agencies worldwide. We also analyze the regulations Latin America countries could apply as starting points to build a robust regulatory framework. This analysis helped us realize where we stand and highlight the weak points that require attention.
We include Brazil, Mexico, Argentina, Colombia, Costa Rica, Dominican Republic, Ecuador, Uruguay, Peru, Chile, and Panama as a representative region sample. We conclude that there is a long way to go and a necessity for international collaboration to achieve standardization in cell treatment regulation. We hope that this review could guide doctors and scientists to improve MSCs production and commercialization. Besides, patients could judge the treatments better when seeking novel or advanced treatments abroad or in their country.
As a highlight, we encourage the community to dismiss the term “stem cells,” as we now know that MSCs in vivo functions are related to the release of bioactive factors into injury or inflammation sites [1] rather than differentiation or engraftment of the infused cells into the damaged tissue. The description of MSCs treatments as “stem cells” leads to confusion and misconceptions among patients and should be avoided, specifically for commercial health care.
The authors of this review work in the field of cell therapy research. A.I.C. is the scientist who first described and named MSCs and has encouraged the change of name to MSCs. He focuses on developing and refining the technology necessary to isolate MSCs. He also integrates basic scientists and clinicians to translate findings into new, innovative human health care protocols more effectively. T.E.O.-S., K.M.-P., A.R.-R., and L.C.L.-M. are currently developing protocols for the isolation and expansion of MSCs following good manufacture practice (GMP) guidelines, including the design of process validation and quality control assessment to eventually translate them into the clinic. Therefore, they have experience in the regulations for the manufacture and clinical application of MSC-based therapies.
Cell-Based Medical Tourism
Medical tourism has increased over the years among those who can pay to receive unavailable, more expensive, or forbidden treatments in their home country. There are many choices with recreational and therapeutic benefits [13]. Many patients travel to countries with underdeveloped medical infrastructures or with less strict regulations regarding health or drugs [15]. Some medical tourism clinics take advantage of the ambiguity or lack of rules to offer their “innovative” treatments without the proper controls [24,25].
Innovative practices include new, untested, or nonstandard procedures prescribed during clinical practice outside research studies [26]. The desire to translate the novel findings into the clinical field has pushed these practices in medical tourism [27]. Also, internet advertising is a critical weakness because of the lack of regulatory surveillance, which needs monitoring and improvement [24].
In some of these clinics, complementary and alternative medicine practitioners, instead of properly trained doctors, administer the treatments [28]. They do not explain the difference between experimental medicines and approved therapeutic products [28,29] or deliberately misinterpret this information [30]. In a few countries, these innovative treatments are available as “compassionate care” of potentially effective therapies for terminally ill patients [15,24].
Nevertheless, the misuse of this designation can represent a potential threat to the patients they serve. Some countries have fought against private clinics that offer unsupported treatments. India, the fifth largest medical tourism destination, created the National Medical and Wellness Tourism Board to formulate guidelines for the sector [17]. Germany, China, and Italy succeeded in reducing or eliminating clinics offering unproven treatments [30]. Nevertheless, those efforts should be not only at a national level but also international [30].
One of the main novel, but scientifically unsubstantiated treatments offered by those medical tourism clinics are MSC-based treatments. Even though MSCs clinical research is still immature, these clinics claim numerous successfully treated patients. These centers do not clarify to the patients the risks of the treatments [13,28,29], and some falsely affirm the treatments represent no risk [29,31]. Clinics offer these cell-based therapies for a broad range of diseases [29], as well as health improvement or esthetic purposes [25,28], without clinical or scientific support [13,32]. These unsubstantiated therapies are popular mainly for conditions in which conventional treatments have poor, limited, or chronic prognoses [24,28,29]. Most of the patients using MSCs want only an improvement in the course of their illness and do not hope for a cure [13].
These patients are at risk of harm, exploitation, or even violations of their autonomy due to nonethical or nonproperly proven therapies [26]. Among the treatments are autologous and allogeneic cells from different origins administered through systemic infusion [13,31]. The most advertised treatment is autologous adipose MSCs transplantation [28,31]. However, a significant number of clinics offering allogeneic treatments have emerged in recent years. While allogeneic MSCs therapy is promising, if not used properly, it can be hazardous. Not surprisingly, the patients have little or no knowledge about the cell source or quality controls in cell isolation, cell cultivation, and delivery of these allogeneic therapies [13,15].
The International Society for Stem Cell Research published a Handbook on Stem Cell Therapies and its clinical translation [33], along with a guideline and a website to provide information for patients regarding cell treatments [32]. Even though this society continuously updates the guidelines to prevent unproven cell therapy use outside clinical trials [15], these guides do not consider health travel precautions or details related to medical tourism [29]. Hence, scientific-based policies regarding cell treatment tourism [24], and health authority surveillance of clinical cell use [15,24,31] and manufacturing processes are urgently needed.
The participation of relevant stakeholders such as the scientific community, policymakers, and regulators is vital to ensure a common benefit [24]. Notably, available information should be accessible. Many clinics do not provide public access to their specific protocols and the information provided is vague, so it is challenging to distinguish between legitimate or unapproved applications [25]. Patients and doctors must understand the hazard of unproven cell therapy [13,31], allogeneic cells cultivated without GMP guidelines, and the documented side effects of some of these therapies [15,32,34,35]. In addition, the data obtained from the regulatory agencies’ inspections of medical tourism centers should become public [24], thus allowing the patients to make an informed decision.
Studies revealed that over 30 intervention locations offered cell-based treatments around the world [28,32]. Despite the highly structured regulatory framework [35], there is a high concentration of “stem cell” clinics in the United States [20,25]. In Germany, Spain, Denmark, the Netherlands, and Italy [20,25,28,36], a smaller number of clinics offer allogeneic therapies as “minimally manipulated” [35,37]. However, the central regions for cell therapy tourism are Asia, Central America, and the Caribbean [15,29,32]. Since language can be a barrier in seeking medical attention [38], researchers for medical tourism often overlook Latin America.
However, some countries in Latin America promote themselves as medical tourism destinations, such as Argentina, Brazil, Costa Rica, Panama [39], and Mexico [17]. Clinics in Central and South America and the Caribbean are famous for offering different cell treatments [29,31,39], and the market in these countries has been growing in recent years and will continue to grow. According to the Latin American Medical Tourism Market Research Report from the Market Data Forecast Webpage, the estimated worth of this market would grow from 7.26 billion USD in 2021 to 17.26 billion USD by 2026 [40].
Due to the highly structured regulatory framework [35], 47 percent of U.S. citizens travel to seek unallowed medical treatments [36]. Furthermore, before establishing their legislative framework, Australia had the highest number of clinics per capita offering these therapies [25]. These data suggest that setting up cell therapy clinics in countries with less stringent regulations is easier and more common. Even though many countries know that unproven therapies are a problem, medical tourism still prevails globally. The costs of adverse effects from an unapproved cell therapy applied abroad are a burden for the travelers’ country of origin. Thus, they must take further action to regulate this practice effectively [32].
Neither governments nor scientists have the power to stop the patients from seeking novel treatments. What remains is to ensure that the treatments offered are safe and effective. One crucial step is knowing the major tourism destinations’ legislative status and encouraging the joint work of the health regulatory bodies worldwide to ensure that homologous regulations are incorporated and guarantee safety for all patients. In the following chapters, we provide an overview of the current legislation regarding cell-based treatments. We focus specially on allogeneic MSC-based treatments because they are among the most dangerous treatments if not manufactured and administer under strict regulation.
MSC-Based Treatment Regulatory Status
Cell therapy involves one of the most complex areas in regulation, and its implementation in the clinical area can overwhelm researchers and health care personnel [41]. Those products have nonuniform characteristics because of their biological heterogeneity, especially on a large scale. To regulate cell-based products according to drug manufacturing standards and assure its quality and effectiveness is complex within a conventional regulatory framework [42]. These products require evaluation criteria outside the traditional scope.
Until now, clinical use of MSCs raises safety and efficacy concerns. Practitioners should not implement it without considering the aspects and guidelines of the health legislation and the development of clinical studies in its different phases [43]. It is the responsibility of national health authorities to ensure that the manufacturing of cell therapy products (CTP) is according to the regulations and to guarantee a safe and ethically liable procurement process.
In addition, the regulators should be sure that their subsequent transfer to the clinical area follows the protocols that they and the ethics committees appropriately authorized [41]. Throughout cell treatments’ history, every country has modified its regulations according to the standardization changes that have been developed, from donor inclusion and exclusion criteria to isolation and manufacturing methods of autologous or allogeneic cell culture products.
The health regulatory authorities commonly denominated as benchmarks are the Food and Drug Administration (FDA) in the United States and the European Medicines Agency (EMA) in the EU. In this study, we also include the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan and the Therapeutic Goods Administration (TGA) in Australia as they are comparable with FDA and EMA [44]. These agencies have established a regulatory framework exclusive for cell therapies used as guide marks by other nations.
Although there are some differences in the definition of human cells or tissue products among these health authorities [45], they all converge that these products contain or consist of human cells or tissues destined for implantation, transplantation, infusion, or transfer to a recipient human being. These products possess pharmacological, immunological, or metabolic properties for treating human beings and prevent diseases [42,45,46]. The terms commonly used for those products are advanced therapy medicinal products (ATMP) [47,48], cell therapy products (CTP) [20], advanced therapy products (ATPs) [49], and cell-based medicinal products [8].
These regulatory bodies consider allogeneic therapy products subjected to substantial manipulation, higher risk, or more than minimally handled products [46,50–52]. This definition covers allogeneic MSCs-based treatments. FDA and EMA classify them as drugs, biological products, or medical devices [35,45,46], PMDA separates them from pharmaceutical and medical devices [42], and TGA defines them as Biological [53].
For this, all regulate the allogeneic cell-based products as tightly as drugs. This regulation includes quality programs in their manufacturing process [45] with compliance of good tissue practices and GMP [45,50]. It also covers the donation, obtaining, evaluation, processing, conservation, storage, distribution, use, manufacturing quality control, traceability, and marketing authorization of human cells and tissues [53–56]. Donor selection is stringently controlled to prevent the introduction, transmission, or spread of communicable diseases [51,57].
In terms of clinical use and before commercialization, these agencies also closely supervise their safety and efficacy [45,54]. Rigorous clinical trials and legal approval are mandatory for all cell therapies [51,54]. The only difference found between these agencies is that the TGA has two schemes for clinical trials: the Clinical Trial Notification, used for early stage studies in which information of preclinical safety studies is available, and the Clinical Trial Application, for high risk or novel treatments [58]. The clinical trial must receive authorization before proceeding [44,52].
As stated before, regulations of the benchmark agencies are well known. For this, we focused our analysis on Latin America’s legislation and examples of international cooperation that can be taken as an example in the region for its harmonization.
Regulation in Latin America
Latin America is comparable with other medical tourism destinations in terms of socioeconomic development, absence of direct regulation, low operating costs, and policies prioritizing provider discretion. These characteristics of the region enable the market of unproven services locally and abroad [37]. Brazil, Mexico, and Costa Rica are among the top 10 medical tourism destinations worldwide [59]. Also, the most active Latin countries in cosmetic procedures are Brazil, México, Argentina, and Colombia [36]. To our knowledge, there are only a few published studies focusing on the cell therapy policies or regulations in Latin America. This knowledge gap limits the understanding of the pros and cons of the industry and obstructs the ability to generate policies favoring health-centered outcomes [59].
According to the Regulation Tracker of the Genetic Literacy Project website, most Latin American countries do not have precise regulations regarding current or future cell therapies [60]. As in other countries, limited funding, resources, and religious background could be hampering cell therapy policymaking [61]. The flourishing of unproven and unethical treatments could promote medical reversal and loss of public trust in cell therapies and resulting therapeutics [26], endangering the conduction of sound research and leading to a decrease in research findings [23]. Awareness of the current legislation status in this region and efforts to standardize cell treatments and harmonize the regulations with the leading health agencies are critical.
As we observed before in the regulations of leading agencies, some of the Latin American countries reviewed in this study considered cell-based products outside of hematopoietic stem cells as biological medicinal products and regulate them as drugs. Their definition and classification of these products, also comparable with the benchmark agencies, can be found in Table 2 [62–66]. Brazil and Costa Rica are the only countries that classify cell therapies according to the level of manipulation and determine that allogeneic-based products are “extensive” or “more than minimal” manipulated [65,67]. Despite differences in the definition of cell therapies, the Latin American agencies agree in the necessity for authorization or licensing of health establishments manipulating cell products.
The licensing helps to guarantee that the establishments would hold the procedures with high sterility and low environmental risk [49,62,67–69]. In some countries, these licenses exist and are used for MSCs collection and banking. Even though the licenses do not grant permission for clinical application, some manufacturers exploit and use them for these procedures.
In the region, Brazil and Argentina are the only countries in which the rules for ATPs are mandatory for cell-based products [49,70]. Nevertheless, every country regulates the procurement, donation, preservation, storage, transport, disposal, traceability, recovery cost, and good practices for organs and tissue products. (Table 2). Generally, these laws are intended for tissue, organ, and bone marrow transplantation [71–75] and do not cover procedures for cell treatments. However, regulators could modify the existing laws to cover these therapies.
In every country, it is mandatory to sign a written informed consent [71–73,76–78], often endorsed by a competent authority [68,77,79,80] for cell donation, and its payment is prohibited [73,76]. Another aspect completely covered is the requirement to obtain data from clinical trials for any new medical product or procedure for its registration, as well as the prohibition of their administration unless evidence from preclinical and clinical trials demonstrates safety and efficacy. These trials must be authorized and supervised by the health authorities [69,81–84].
We enlisted definitions, classifications, and regulations for different critical processes for manufacture of ATMPs in the Latin American countries selected in this review in Table 2 and further describe the main aspects of the legislation in each of the reviewed countries. As some regulatory bodies in Latin America do not consider cell therapies in their legal framework, the policy makers in there are promoting draft standards. These laws will be reviewed independently next so patients and practitioners could consider them before the extensive use of any treatment, including cell-based products
México
Mexico, after Thailand, is the second largest medical tourism market because of its proximity to the United States and the lack of stringent regulations. It attracts over a million medical tourists a year, especially for regenerative medicine and cell therapies. Many clinics are advertised and based in the United States, but provide their treatments in Mexico due to the permissive regulations for several innovative practices. As in most Latin American countries, the lack of international laws and inadequate support for local health authorities to enforce existing legal and ethical guidelines have promoted these practices.
The health agency in this country is the Federal Commission for the Protection against Sanitary Risks (COFEPRIS, “Comisión Federal de Protección contra Riesgos Sanitarios”). In contrast to Brazil and Argentina, there is no regulatory framework regarding cell-based treatments. For these, policy makers have presented a draft standard for the implantation of progenitor cells for therapeutic and research purposes. However, it does not consider or classify cell therapies other than hematopoietic stem cells or blood components, and until now, it has not been officially released.
COFEPRIS does not officially regulate cell-based therapies as procedures or drugs; nevertheless, according to the arisen needs with the emergence of “regenerative medicine” clinics and several establishments processing cells and tissues, it issues licenses for procurement, isolation, or preserving stem and progenitor cells. Another license, called “Regenerative Medicine,” allows the application of platelet-rich plasma and other autologous procedures. However, it does not forbid any specific application, creating an ambiguity abused by many. According to several studies, clinics in Mexico are more likely to offer allogeneic therapies, probably using the Regenerative Medicine license. Yet, there are still an important number of clinics that are unlicensed by COFEPRIS offering these treatments.
Health establishments should satisfy the Statutes of the General Health Law and the guidelines published by the Transplant National Center (CENATRA, “Centro Nacional de Transplantes”) before tissue procurement and cell transplantation. Furthermore, the National Center for Blood Transfusion (CNTS, “Centro Nacional de Transfusión Sanguínea”) requires a monthly report of every cell donation, preservation, and transplant.
Although the authority requests it, these requirements are not established in any regulation or standard and are not legally required. Also, these principles seem contradictory since cell transplantation is not considered a blood transfusion. CENATRA, in the Statutes of the Control of Organs, excludes progenitor cells without explaining which cells are “progenitor.” We found this confusion as an improvement opportunity within the Mexican regulation that requires the attention and collaboration of stakeholders and researchers.
Currently, COFEPRIS demands the health establishments processing cells to adhere to the Official Norms designed for blood or tissue management for the clinical and laboratory screening of the donor: NOM-253-SSA2-2012, for the manipulation of human blood and its components for therapeutic purposes; and NOM-039-SSA2-2014, for the prevention and control of sexually transmitted infections. In addition, every new medical product should be subjected to clinical trials before authorization as a therapy, according to NOM-012-SSA3-2012 criteria for the execution of research projects for human health and the Statutes of the General Health Law in matters of Research for Health. COFEPRIS is also suggesting the use of other standards initially designed for drugs to simulate a regulatory framework resembling the benchmarks.
If the establishment wants to administer the MSC product in a patient, it should request the license for the industry or laboratory of medicines or biological products for human use and a Certification of GMP for Health Supplies to manufacture allogeneic MSC-based products, and its manufacture must be performed following NOM-059-SSA1-2015, good manufacturing practices for medicine, and NOM-164-SSA1-2015, good manufacturing practices for drugs. However, all these are mere suggestions and therefore are not routinely required when asking for a Regenerative Medicine or Stem Cell Bank license.
Mexican cell therapy-related regulations need further efforts such as cell therapy definitions, classification, and considering additional quality controls in every step of the manufacturing process. Continuous inspections are critical to avoid using the licenses mentioned above for cell therapy administration without proper testing. COFEPRIS has declared that one of the primary oversight tools is the patient’s reports to regulatory authorities. However, this is an unpopular practice. First, because many patients do not have the tools to assess scientific legitimacy, and second, many seek experimental procedures that are broadly prohibited
International Cooperation for Standardization
The international community has made several endeavors to homologate the regulation of cell-based treatments. The ATMP cluster of FDA-EMA-Health Canada has focused on the convergence of regulatory protocols in the United States, EU, and Canada. Another example is the Cell Therapy Working Group of the International Pharmaceutical Regulators Forum, which includes Australia, New Zealand, Singapore, Taiwan, and South Korea [19]. In Asia, the Forum for Innovative Regenerative Medicine in Japan aims to develop an optimized and homogeneous regulatory framework for the clinical application of Regenerative Medicine products and expedite the distribution of those products among Asian markets. China, Korea, India, Singapore, and Taiwan are participating in this initiative [104].
The international health agency for the Americas, the Pan American Health Organization (PAHO), issued the “Regulation of advanced therapy medicinal products: concept note and recommendations,” aimed to highlight the progress made in ATPs, their risks, and the regulatory challenges for the Member States to strengthen regulatory systems and a call to action for governments to control unapproved therapies [105].
This document defines ATMPs to be medicines for human use, obtained from cells (cell therapy), genes (gene therapy), or tissue (tissue engineering), including products of autologous, allogeneic, and xenogeneic origin. Also, it considers that cell therapy should be classified as minimal or substantial manipulation [105]. Along with the guides of FDA and EMA regulations, several countries in America can use this document as the basis for regulatory development around ATMPs.
Several regions or clusters of countries implemented international cooperation to standardize regulation for these treatments. Further, the authorities could apply National and Subregional Technical Regulations that oversee the manufacture, GMP compliance, commercialization, marketing approval, registration, authorization, and quality control of drugs for allogeneic MSCs products [62–64].
Another way to achieve global legislative standardization is to consider the global rules for organ and tissue transplantation established by the World Health Organization (WHO). As an approach to develop international regulations, it released a list of follow-up principles for obtaining organs from various sources and their restrictions [106]. It also published a report of the First Global Consultation on Regulatory Requirements for Human Cells and Tissues for Transplantation, for harmonizing global practices in the procurement, processing, and transplantation of human cells and tissues [107] and the screening of donated blood for transfusion-transmissible infections: recommendations.
Those documents aimed to support countries in establishing effective screening programs to protect the recipients from transmissible infections [108] and could be used as a reference point in nations where regulation does not consider ATMPs [20].
The processes for harmonization have evolved from a pharmaceutical model and evidence-based medicine to facilitate particular forms of global cell governance and allow national regulators to adopt local capacities and strategies to international standards. Altering standardization politics with alternative methods and evidence for clinical innovation has emerged to reduce clinical testing costs and increase access to nonsystematically proven innovative interventions at an earlier stage. Examples of this are the growing number of regulatory exceptions, market authorization after early-phase clinical trials, or regulatory adjustments for the claimed right-to-try of the patients [19,89,109].
As this article has shown, and despite the efforts, international harmonization of the regulatory landscape of cell-based treatments has faced an increasing process of regulatory diversification. How governments and international scientific communities respond to the regulatory challenges is critical for developing more and improved allogeneic CTP.
Conclusion
Although MSC therapy could change the practice of medicine, there are several concerns to be solved before their routine use in the clinics. As MSCs therapies become popular, the hazard of obtaining an unapproved, unethical, and possibly dangerous treatment is high, particularly regarding allogeneic-based products. The lack of regulations and medical tourism complicates the situation. Another substantial risk is that the public perception of innovative practices could mislead the translating of basic knowledge into clinics without the proper controls, increasing the possibility of crowding out research. This risk is especially critical in developing or low- and middle-income countries, where the financial and public support of science and research are already low.
Cell tourism market is increasing in several countries of Latin America, especially in Mexico, the second most popular destination in the world. The U.S. proximity and the lack of regulations regarding cell therapies have favored this. In our analysis, we observe heterogenicity in the legislation regarding cell-based treatments. Some countries in the region recognize allogeneic cell therapies as a medical procedure, while others regulated them as a biological drug, as in the benchmarks of regulation.
Along with the legislation in every country, international cooperation is required to continuously evolve regulations to establish a homologous criterion to obtain safe MSC-based products that could be used worldwide and encourage new, ethical, and better technologies without neglecting the patients’ needs. International cooperation efforts to achieve standardization are being implemented, but creating a centralized source of information for regulation seems necessary in every region.
On the other hand, patients should be able to discriminate between unproven and supported therapies to determine the best option for their treatment. As researchers and medical practitioners, it is our responsibility to inform society about the new technologies and products available and prevent them from dangers of unapproved, broadly advertised treatments.
Acknowledgments
Authors want to thank Blanca Fabiola Fajardo-Fregoso for the proofreading and constructive feedback.
Author Disclosure Statement
L.C.L.-M., T.E.O.-S., K.M.-P., and A.R.-R. are employees in the Stem Cell Bank, Provida Salud Integral. A.I.C. is a paid scientific consultant in CryoVida, Banco de Células Madre Adultas.
Funding Information
No funding was received for this article.
